Growth Hormone Deficiency: Causes, Symptoms & Diagnosis – Healthline

A growth hormone deficiency (GHD) occurs when the pituitary gland doesnt produce enough growth hormone. It affects children more often than adults.

The pituitary gland is a small gland about the size of a pea. Its located at the base of the skull and secretes eight hormones. Some of these hormones control thyroid activity and body temperature.

GHD occurs in roughly 1 out of 7,000 births. The condition is also a symptom of several genetic diseases, including Prader-Willi syndrome.

You may be concerned that your child isnt meeting height and weight growth standards. But if its GHD, its important to know that its treatable. Children who are diagnosed early often recover very well. If left untreated, the condition can result in shorter-than-average height and delayed puberty.

Your body still needs growth hormone after youve finished puberty. Once youre in adulthood, the growth hormone maintains your body structure and metabolism. Adults can also develop GHD, but it isnt as common.

GHD that isnt present at birth may be caused by a tumor in the brain. These tumors are normally located at the site of the pituitary gland or the nearby hypothalamus region of the brain.

In children and adults, serious head injuries, infections, and radiation treatments can also cause GHD. This is called acquired growth hormone deficiency (AGHD).

Most cases of GHD are idiopathic, meaning that no cause has yet been found.

Children with GHD are shorter than their peers and have younger-looking, rounder faces. They may also have baby fat around the abdomen, even though their body proportions are average.

If GHD develops later in a childs life, such as from a brain injury or tumor, its main symptom is delayed puberty. In some instances, sexual development is halted.

Many teens with GHD experience low self-esteem due to developmental delays, such as short stature or a slow rate of maturing. For example, young women may not develop breasts and young mens voices may not change at the same rate as their peers.

Reduced bone strength is another symptom of AGHD. This may lead to more frequent fractures, especially in older adults.

People with low growth hormone levels may feel tired and lack stamina. They may experience sensitivity to hot or cold temperatures.

Those with GHD may experience certain psychological effects, including:

Adults with AGHD typically have high levels of fat in the blood and high cholesterol. This isnt due to poor diet, but rather to changes in the bodys metabolism caused by low levels of growth hormone. Adults with AGHD are at greater risk for diabetes and heart disease.

Your childs doctor will look for signs of GHD if your child isnt meeting their height and weight milestones. Theyll ask you about your growth rate as you approached puberty, as well as your other childrens growth rates. If they suspect GHD, a number of tests can confirm the diagnosis.

Your levels of growth hormone fluctuate widely throughout the day and night (diurnal variation). A blood test with a lower-than-normal result isnt enough evidence in itself to make a diagnosis.

One blood test can measure levels of proteins which are markers of growth hormone function but are much more stable. These are IGF-1 (insulin-like growth factor 1) and IGFPB-3 (insulin-like growth factor binding protein 3).

Your doctor may then go on to a GH stimulation test, if screening tests suggest that you have a GH deficiency.

Growth plates are the developing tissue at each end of your arm and leg bones. Growth plates fuse together when youve finished developing. X-rays of your childs hand can indicate their level of bone growth.

If a childs bone age is younger than their chronological age, this might be due to GHD.

If your doctor suspects a tumor or other damage to the pituitary gland, an MRI imaging scan can provide a detailed look inside the brain. Growth hormone levels will often be screened in adults who have a history of pituitary disorders, a brain injury, or who need brain surgery.

Testing can determine whether the pituitary condition was present at birth or brought on by an injury or tumor.

Since the mid-1980s, synthetic growth hormones have been used with great success to treat children and adults. Before synthetic growth hormones, natural growth hormones from cadavers were used for treatment.

Growth hormone is given by injection, typically into the bodys fatty tissues, such as the back of the arms, thighs, or buttocks. Its most effective as a daily treatment.

Side effects are generally minor, but may include:

In rare cases, long-term growth hormone injections may contribute to the development of diabetes, especially in people with a family history of that disease.

Children with congenital GHD are often treated with growth hormone until they reach puberty. Often, children who have too little growth hormone in their youth will naturally begin to produce enough as they enter adulthood.

However, some remain in treatment for their entire lives. Your doctor can determine whether you need ongoing injections by monitoring hormone levels in your blood.

Make an appointment with your doctor if you suspect that you or your child is deficient in growth hormones.

Many people respond very well to treatment. The sooner you start treatment, the better your results will be.

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Growth Hormone Deficiency: Causes, Symptoms & Diagnosis - Healthline

Plant hormone – Wikipedia

Chemical compounds that regulate plant growth and development

Plant hormone (or phytohormones) are signal molecules, produced within plants, that occur in extremely low concentrations. Plant hormones control all aspects of plant growth and development, from embryogenesis,[1] the regulation of organ size, pathogen defense,[2][3] stress tolerance[4][5] and through to reproductive development.[6] Unlike in animals (in which hormone production is restricted to specialized glands) each plant cell is capable of producing hormones.[7][8] Went and Thimann coined the term "phytohormone" and used it in the title of their 1937 book.[9]

Phytohormones occur across the plant kingdom, and even in algae, where they have similar functions to those seen in higher plants.[10] Some phytohormones also occur in microorganisms, such as unicellular fungi and bacteria, however in these cases they do not play a hormonal role and can better be regarded as secondary metabolites.[11]

The word hormone is derived from Greek, meaning set in motion. Plant hormones affect gene expression and transcription levels, cellular division, and growth. They are naturally produced within plants, though very similar chemicals are produced by fungi and bacteria that can also affect plant growth.[12] A large number of related chemical compounds are synthesized by humans. They are used to regulate the growth of cultivated plants, weeds, and in vitro-grown plants and plant cells; these manmade compounds are called plant growth regulators (PGRs). Early in the study of plant hormones, "phytohormone" was the commonly used term, but its use is less widely applied now.

Plant hormones are not nutrients, but chemicals that in small amounts promote and influence the growth,[13] development, and differentiation of cells and tissues. The biosynthesis of plant hormones within plant tissues is often diffuse and not always localized. Plants lack glands to produce and store hormones, because, unlike animalswhich have two circulatory systems (lymphatic and cardiovascular) powered by a heart that moves fluids around the bodyplants use more passive means to move chemicals around their bodies. Plants utilize simple chemicals as hormones, which move more easily through their tissues. They are often produced and used on a local basis within the plant body. Plant cells produce hormones that affect even different regions of the cell producing the hormone.

Hormones are transported within the plant by utilizing four types of movements. For localized movement, cytoplasmic streaming within cells and slow diffusion of ions and molecules between cells are utilized. Vascular tissues are used to move hormones from one part of the plant to another; these include sieve tubes or phloem that move sugars from the leaves to the roots and flowers, and xylem that moves water and mineral solutes from the roots to the foliage.

Not all plant cells respond to hormones, but those cells that do are programmed to respond at specific points in their growth cycle. The greatest effects occur at specific stages during the cell's life, with diminished effects occurring before or after this period. Plants need hormones at very specific times during plant growth and at specific locations. They also need to disengage the effects that hormones have when they are no longer needed. The production of hormones occurs very often at sites of active growth within the meristems, before cells have fully differentiated. After production, they are sometimes moved to other parts of the plant, where they cause an immediate effect; or they can be stored in cells to be released later. Plants use different pathways to regulate internal hormone quantities and moderate their effects; they can regulate the amount of chemicals used to biosynthesize hormones. They can store them in cells, inactivate them, or cannibalise already-formed hormones by conjugating them with carbohydrates, amino acids, or peptides. Plants can also break down hormones chemically, effectively destroying them. Plant hormones frequently regulate the concentrations of other plant hormones.[14] Plants also move hormones around the plant diluting their concentrations.

The concentration of hormones required for plant responses are very low (106 to 105 mol/L). Because of these low concentrations, it has been very difficult to study plant hormones, and only since the late 1970s have scientists been able to start piecing together their effects and relationships to plant physiology.[15] Much of the early work on plant hormones involved studying plants that were genetically deficient in one or involved the use of tissue-cultured plants grown in vitro that were subjected to differing ratios of hormones, and the resultant growth compared. The earliest scientific observation and study dates to the 1880s; the determination and observation of plant hormones and their identification was spread out over the next 70 years.

Different hormones can be sorted into different classes, depending on their chemical structures. Within each class of hormone, chemical structures can vary, but all members of the same class have similar physiological effects. Initial research into plant hormones identified five major classes: abscisic acid, auxins, brassinosteroids, cytokinins and ethylene.[16] This list was later expanded, and brassinosteroids, jasmonates, salicylic acid, and strigolactones are now also considered major plant hormones. Additionally there are several other compounds that serve functions similar to the major hormones, but their status as bona fide hormones is still debated.

Abscisic acid (also called ABA) is one of the most important plant growth inhibitors. It was discovered and researched under two different names, dormin and abscicin II, before its chemical properties were fully known. Once it was determined that the two compounds are the same, it was named abscisic acid. The name refers to the fact that it is found in high concentrations in newly abscissed or freshly fallen leaves.

This class of PGR is composed of one chemical compound normally produced in the leaves of plants, originating from chloroplasts, especially when plants are under stress. In general, it acts as an inhibitory chemical compound that affects bud growth, and seed and bud dormancy. It mediates changes within the apical meristem, causing bud dormancy and the alteration of the last set of leaves into protective bud covers. Since it was found in freshly abscissed leaves, it was initially thought to play a role in the processes of natural leaf drop, but further research has disproven this. In plant species from temperate parts of the world, abscisic acid plays a role in leaf and seed dormancy by inhibiting growth, but, as it is dissipated from seeds or buds, growth begins. In other plants, as ABA levels decrease, growth then commences as gibberellin levels increase. Without ABA, buds and seeds would start to grow during warm periods in winter and would be killed when it froze again. Since ABA dissipates slowly from the tissues and its effects take time to be offset by other plant hormones, there is a delay in physiological pathways that provides some protection from premature growth. Abscisic acid accumulates within seeds during fruit maturation, preventing seed germination within the fruit or before winter. Abscisic acid's effects are degraded within plant tissues during cold temperatures or by its removal by water washing in and out of the tissues, releasing the seeds and buds from dormancy.[17]

ABA exists in all parts of the plant, and its concentration within any tissue seems to mediate its effects and function as a hormone; its degradation, or more properly catabolism, within the plant affects metabolic reactions and cellular growth and production of other hormones.[18] Plants start life as a seed with high ABA levels. Just before the seed germinates, ABA levels decrease; during germination and early growth of the seedling, ABA levels decrease even more. As plants begin to produce shoots with fully functional leaves, ABA levels begin to increase again, slowing down cellular growth in more "mature" areas of the plant. Stress from water or predation affects ABA production and catabolism rates, mediating another cascade of effects that trigger specific responses from targeted cells. Scientists are still piecing together the complex interactions and effects of this and other phytohormones.

In plants under water stress, ABA plays a role in closing the stomata. Soon after plants are water-stressed and the roots are deficient in water, a signal moves up to the leaves, causing the formation of ABA precursors there, which then move to the roots. The roots then release ABA, which is translocated to the foliage through the vascular system[19] and modulates potassium and sodium uptake within the guard cells, which then lose turgidity, closing the stomata.[20][21]

Auxins are compounds that positively influence cell enlargement, bud formation, and root initiation. They also promote the production of other hormones and, in conjunction with cytokinins, control the growth of stems, roots, and fruits, and convert stems into flowers.[22] Auxins were the first class of growth regulators discovered.A Dutch Biologist Frits Warmolt Went first described auxins.[23] They affect cell elongation by altering cell wall plasticity. They stimulate cambium, a subtype of meristem cells, to divide, and in stems cause secondary xylem to differentiate.

Auxins act to inhibit the growth of buds lower down the stems in a phenomenon known as apical dominance, and also to promote lateral and adventitious root development and growth. Leaf abscission is initiated by the growing point of a plant ceasing to produce auxins. Auxins in seeds regulate specific protein synthesis,[24] as they develop within the flower after pollination, causing the flower to develop a fruit to contain the developing seeds.

In large concentrations, auxins are often toxic to plants; they are most toxic to dicots and less so to monocots. Because of this property, synthetic auxin herbicides including 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) have been developed and used for weed control by defoliation. Auxins, especially 1-naphthaleneacetic acid (NAA) and indole-3-butyric acid (IBA), are also commonly applied to stimulate root growth when taking cuttings of plants. The most common auxin found in plants is indole-3-acetic acid (IAA).

Brassinosteroids are a class of polyhydroxysteroids, the only example of steroid-based hormones in plants. Brassinosteroids control cell elongation and division, gravitropism, resistance to stress, and xylem differentiation. They inhibit root growth and leaf abscission. Brassinolide was the first identified brassinosteroid and was isolated from extracts of rapeseed (Brassica napus) pollen in 1979.[25] Brassinosteroids are a class of steroidal phytohormones in plants that regulate numerous physiological processes. This plant hormone was identified by Mitchell et al. who extracted ingredients from Brassica pollen only to find that the extracted ingredients main active component was Brassinolide.[26] This finding meant the discovery of a new class of plant hormones called Brassinosteroids. These hormones act very similarly to animal steroidal hormones by promoting growth and development. In plants these steroidal hormones play an important role in cell elongation via BR signaling.[27] Brassinosteroids receptor- brassinosteroid insensitive 1 (BRI1) is the main receptor for this signaling pathway. This BRI1 receptor was found by Clouse et al. who made the discovery by inhibiting BR and comparing it to the wildtype in Arabidopsis. The BRI1 mutant displayed several problems associated with growth and development such as dwarfism, reduced cell elongation and other physical alterations.[26] These findings mean that plants properly expressing brassinosteroids grow more than their mutant counterparts. Brassinosteroids bind to BRI1 localized at the plasma membrane[28] which leads to a signal cascade that further regulates cell elongation. This signal cascade however is not entirely understood at this time. What is believed to be happening is that BR binds to the BAK1 complex which leads to a phosphorylation cascade.[29] This phosphorylation cascade then causes BIN2 to be deactivated which causes the release of transcription factors.[29] These released transcription factors then bind to DNA that leads to growth and developmental processes [29] and allows plants to respond to abiotic stressors.[30]

Cytokinins or CKs are a group of chemicals that influence cell division and shoot formation. They also help delay senescence of tissues, are responsible for mediating auxin transport throughout the plant, and affect internodal length and leaf growth. They were called kinins in the past when they were first isolated from yeast cells. Cytokinins and auxins often work together, and the ratios of these two groups of plant hormones affect most major growth periods during a plant's lifetime. Cytokinins counter the apical dominance induced by auxins; in conjunction with ethylene, they promote abscission of leaves, flower parts, and fruits.[31]

Among the plant hormones, the 3 that are known to help with immunological interactions are ethylene (ET), salicylates (SA), and jasmonates (JA), however more research has gone into identifying the role that cytokinins (CK) play in this. Evidence suggests that cytokinins delay the interactions with pathogens, showing signs that they could induce resistance toward these pathogenic bacteria. Accordingly, there are higher CK levels in plants that have increased resistance to pathogens compared to those which are more susceptible.[32] For example, pathogen resistance involving cytokinins was tested using the Arabidopsis species by treating them with naturally occurring CK (trans-zeatin) to see their response to the bacteria Pseudomonas syringa. Tobacco studies reveal that over expression of CK inducing IPT genes yields increased resistance whereas over expression of CK oxidase yields increased susceptibility to pathogen, namely P. syringae.

While theres not much of a relationship between this hormone and physical plant behavior, there are behavioral changes that go on inside the plant in response to it. Cytokinin defense effects can include the establishment and growth of microbes (delay leaf senescence), reconfiguration of secondary metabolism or even induce the production of new organs such as galls or nodules.[33] These organs and their corresponding processes are all used to protect the plants against biotic/abiotic factors.

Unlike the other major plant hormones, ethylene is a gas and a very simple organic compound, consisting of just six atoms. It forms through the breakdown of methionine, an amino acid which is in all cells. Ethylene has very limited solubility in water and therefore does not accumulate within the cell, typically diffusing out of the cell and escaping the plant. Its effectiveness as a plant hormone is dependent on its rate of production versus its rate of escaping into the atmosphere. Ethylene is produced at a faster rate in rapidly growing and dividing cells, especially in darkness. New growth and newly germinated seedlings produce more ethylene than can escape the plant, which leads to elevated amounts of ethylene, inhibiting leaf expansion (see hyponastic response).

As the new shoot is exposed to light, reactions mediated by phytochrome in the plant's cells produce a signal for ethylene production to decrease, allowing leaf expansion. Ethylene affects cell growth and cell shape; when a growing shoot or root hits an obstacle while underground, ethylene production greatly increases, preventing cell elongation and causing the stem to swell. The resulting thicker stem is stronger and less likely to buckle under pressure as it presses against the object impeding its path to the surface. If the shoot does not reach the surface and the ethylene stimulus becomes prolonged, it affects the stem's natural geotropic response, which is to grow upright, allowing it to grow around an object. Studies seem to indicate that ethylene affects stem diameter and height: when stems of trees are subjected to wind, causing lateral stress, greater ethylene production occurs, resulting in thicker, sturdier tree trunks and branches.

Ethylene also affects fruit ripening. Normally, when the seeds are mature, ethylene production increases and builds up within the fruit, resulting in a climacteric event just before seed dispersal. The nuclear protein Ethylene Insensitive2 (EIN2) is regulated by ethylene production, and, in turn, regulates other hormones including ABA and stress hormones.[34] Ethylene diffusion out of plants is strongly inhibited underwater. This increases internal concentrations of the gas. In numerous aquatic and semi-aquatic species (e.g. Callitriche platycarpus, rice, and Rumex palustris), the accumulated ethylene strongly stimulates upward elongation. This response is an important mechanism for the adaptive escape from submergence that avoids asphyxiation by returning the shoot and leaves to contact with the air whilst allowing the release of entrapped ethylene.[35][36][37][38] At least one species (Potamogeton pectinatus)[39] has been found to be incapable of making ethylene while retaining a conventional morphology. This suggests ethylene is a true regulator rather than being a requirement for building a plant's basic body plan.

Gibberellins (GAs) include a large range of chemicals that are produced naturally within plants and by fungi. They were first discovered when Japanese researchers, including Eiichi Kurosawa, noticed a chemical produced by a fungus called Gibberella fujikuroi that produced abnormal growth in rice plants.[40] It was later discovered that GAs are also produced by the plants themselves and control multiple aspects of development across the life cycle. The synthesis of GA is strongly upregulated in seeds at germination and its presence is required for germination to occur. In seedlings and adults, GAs strongly promote cell elongation. GAs also promote the transition between vegetative and reproductive growth and are also required for pollen function during fertilization.[41]

Gibberellins breaks the dormancy (in active stage) in seeds and buds and helps increasing the height of the plant. It helps in the growth of the stem[citation needed]

Jasmonates (JAs) are lipid-based hormones that were originally isolated from jasmine oil.[42] JAs are especially important in the plant response to attack from herbivores and necrotrophic pathogens.[43] The most active JA in plants is jasmonic acid. Jasmonic acid can be further metabolized into methyl jasmonate (MeJA), which is a volatile organic compound. This unusual property means that MeJA can act as an airborne signal to communicate herbivore attack to other distant leaves within one plant and even as a signal to neighboring plants.[44] In addition to their role in defense, JAs are also believed to play roles in seed germination, the storage of protein in seeds, and root growth.[43]

JAs have been shown to interact in the signalling pathway of other hormones in a mechanism described as crosstalk. The hormone classes can have both negative and positive effects on each other's signal processes.[45]

Jasmonic acid methyl ester (JAME) has been shown to regulate genetic expression in plants.[46] They act in signalling pathways in response to herbivory, and upregulate expression of defense genes.[47] Jasmonyl-isoleucine (JA-Ile) accumulates in response to herbivory, which causes an upregulation in defense gene expression by freeing up transcription factors.[47]

Jasmonate mutants are more readily consumed by herbivores than wild type plants, indicating that JAs play an important role in the execution of plant defense. When herbivores are moved around leaves of wild type plants, they reach similar masses to herbivores that consume only mutant plants, implying the effects of JAs are localized to sites of herbivory.[48] Studies have shown that there is significant crosstalk between defense pathways.[49]

Salicylic acid (SA) is a hormone with a structure related to phenol. It was originally isolated from an extract of white willow bark (Salix alba) and is of great interest to human medicine, as it is the precursor of the painkiller aspirin. In plants, SA plays a critical role in the defense against biotrophic pathogens. In a similar manner to JA, SA can also become methylated. Like MeJA, methyl salicylate is volatile and can act as a long-distance signal to neighboring plants to warn of pathogen attack. In addition to its role in defense, SA is also involved in the response of plants to abiotic stress, particularly from drought, extreme temperatures, heavy metals, and osmotic stress.[50]

Salicylic acid (SA) serves as a key hormone in plant innate immunity, including resistance in both local and systemic tissue upon biotic attacks, hypersensitive responses, and cell death. Some of the SA influences on plants include seed germination, cell growth, respiration, stomatal closure, senescence-associated gene expression, responses to abiotic and biotic stresses, basal thermo tolerance and fruit yield. A possible role of salicylic acid in signaling disease resistance was first demonstrated by injecting leaves of resistant tobacco with SA.[51] The result was that injecting SA stimulated pathogenesis related (PR) protein accumulation and enhanced resistance to tobacco mosaic virus (TMV) infection. Exposure to pathogens causes a cascade of reactions in the plant cells. SA biosynthesis is increased via isochorismate synthase (ICS) and phenylalanine ammonia-lyase (PAL) pathway in plastids.[52] It was observed that during plant-microbe interactions, as part of the defense mechanisms, SA is initially accumulated at the local infected tissue and then spread all over the plant to induce systemic acquired resistance at non-infected distal parts of the plant. Therefore with increased internal concentration of SA, plants were able to build resistant barriers for pathogens and other adverse environmental conditions[53]

Strigolactones (SLs) were originally discovered through studies of the germination of the parasitic weed Striga lutea. It was found that the germination of Striga species was stimulated by the presence of a compound exuded by the roots of its host plant.[54] It was later shown that SLs that are exuded into the soil also promote the growth of symbiotic arbuscular mycorrhizal (AM) fungi.[55] More recently, another role of SLs was identified in the inhibition of shoot branching.[56] This discovery of the role of SLs in shoot branching led to a dramatic increase in the interest in these hormones, and it has since been shown that SLs play important roles in leaf senescence, phosphate starvation response, salt tolerance, and light signalling.[57]

Other identified plant growth regulators include:

Synthetic plant hormones or PGRs are used in a number of different techniques involving plant propagation from cuttings, grafting, micropropagation and tissue culture. Most commonly they are commercially available as "rooting hormone powder".

The propagation of plants by cuttings of fully developed leaves, stems, or roots is performed by gardeners utilizing auxin as a rooting compound applied to the cut surface; the auxins are taken into the plant and promote root initiation. In grafting, auxin promotes callus tissue formation, which joins the surfaces of the graft together. In micropropagation, different PGRs are used to promote multiplication and then rooting of new plantlets. In the tissue-culturing of plant cells, PGRs are used to produce callus growth, multiplication, and rooting.

Plant hormones affect seed germination and dormancy by acting on different parts of the seed.

Embryo dormancy is characterized by a high ABA:GA ratio, whereas the seed has high abscisic acid sensitivity and low GA sensitivity. In order to release the seed from this type of dormancy and initiate seed germination, an alteration in hormone biosynthesis and degradation toward a low ABA/GA ratio, along with a decrease in ABA sensitivity and an increase in GA sensitivity, must occur.

ABA controls embryo dormancy, and GA embryo germination.Seed coat dormancy involves the mechanical restriction of the seed coat. This, along with a low embryo growth potential, effectively produces seed dormancy. GA releases this dormancy by increasing the embryo growth potential, and/or weakening the seed coat so the radical of the seedling can break through the seed coat.Different types of seed coats can be made up of living or dead cells, and both types can be influenced by hormones; those composed of living cells are acted upon after seed formation, whereas the seed coats composed of dead cells can be influenced by hormones during the formation of the seed coat. ABA affects testa or seed coat growth characteristics, including thickness, and effects the GA-mediated embryo growth potential. These conditions and effects occur during the formation of the seed, often in response to environmental conditions. Hormones also mediate endosperm dormancy: Endosperm in most seeds is composed of living tissue that can actively respond to hormones generated by the embryo. The endosperm often acts as a barrier to seed germination, playing a part in seed coat dormancy or in the germination process. Living cells respond to and also affect the ABA:GA ratio, and mediate cellular sensitivity; GA thus increases the embryo growth potential and can promote endosperm weakening. GA also affects both ABA-independent and ABA-inhibiting processes within the endosperm.[66]

Willow bark has been used for centuries as a painkiller. The active ingredient in willow bark that provides these effects is the hormone salicylic acid (SA). In 1899, the pharmaceutical company Bayer began marketing a derivative of SA as the drug aspirin.[67] In addition to its use as a painkiller, SA is also used in topical treatments of several skin conditions, including acne, warts and psoriasis.[68] Another derivative of SA, sodium salicylate has been found to suppress proliferation of lymphoblastic leukemia, prostate, breast, and melanoma human cancer cells.[69]

Jasmonic acid (JA) can induce death in lymphoblastic leukemia cells. Methyl jasmonate (a derivative of JA, also found in plants) has been shown to inhibit proliferation in a number of cancer cell lines,[69] although there is still debate over its use as an anti-cancer drug, due to its potential negative effects on healthy cells.[70]

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Plant hormone - Wikipedia

Andy Pettitte’s 2007 take on PED use: "I tried HGH. Though it was not against baseball rules, I was not comfortable with what I was doing" -…

Andy Pettitte's 2007 take on PED use: "I tried HGH. Though it was not against baseball rules, I was not comfortable with what I was doing"  Sportskeeda

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New HGH CEO and Chair discuss staff shortages and other health care challenges – The Review Newspaper

New HGH CEO and Chair discuss staff shortages and other health care challenges  The Review Newspaper

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New HGH CEO and Chair discuss staff shortages and other health care challenges - The Review Newspaper

10 Foods That Increase Human Growth Hormone – Medicalopedia

These 10 foods that increase human growth hormone can help boost both HGH (human growth hormone) and testosterone levels. Find out which 10 foods made our list of human growth hormone boosters.

The food you eat today could increase or decrease your human growth hormone levels tomorrow. When talking about hormone production, the saying you are what you eat has never been more relevant. These 10 foods that increase human growth hormone not only help raise HGH levels but many of them will impact testosterone production, as well.

Just think, something that you eat right before bedtime can improve sleep and increase energy. It can help you lose weight, remember facts more clearly, and even strengthen your bones. By knowing which foods to increase human growth hormone that you should eat, and when, you can change the way you look and feel.

Of course, you do not have to eat all 10 foods on our list below on the same day. However, the more of them that you can incorporate into your daily diet, the better the chance of avoiding HGH therapy to treat growth hormone deficiency.

Here is our list of the top 10 foods that increase human growth hormone naturally:

Goji Berries filled with 18 amino acids, 22 minerals, fatty acids, vitamins, and Sesquiterpenoids (phytonutrient), goji berries top the list of HGH stimulators.

Pineapple enjoy at bedtime to boost melatonin and serotonin release that will help you sleep. Pineapple is a digestion aid that also increases fat burning which occurs with the help of HGH while you sleep. A bonus is that pineapple also boosts testosterone production at night.

Fava Beans these tiny beans sit high on the HGH boosting list because they are packed with L-Dopa. Along with increasing testosterone and dopamine levels, fava beans also contain zinc, vitamin B6, magnesium, potassium, and other minerals.

Coconut Oil with many health benefits, its ability to spike a surge of HGH within a 30 90-minute period after consumption makes it a go-to booster.

Yogurt unpasteurized, organic yogurt contains L-glutamine to boost HGH levels.

Eggs organic, free-range eggs are loaded with vitamins and growth factors that boost HGH and testosterone levels.

Grassfed Beef considered a superfood, grass-fed beef contains bio-active amino acids, carnitine, and Co-Q10 to help stimulate a significant HGH boost.

Raw Chocolate loaded with more tryptophan than turkey, raw chocolate (not milk or white types) increases dopamine. You will sleep better and see a massive boost in both HGH and testosterone levels from raw cacao.

Nuts high in L-arginine, nuts not only help increase HGH but also improve fat-burning for weight loss.

Watermelon this fruit contains L-citrulline, an amino acid that the body converts to arginine to increase HGH secretion.

Why Does Food Have an Impact on Human Growth Hormone?

These foods that increase human growth hormone work in many ways. More than half your daily allotment of HGH secretion occurs while you are in a state of deep, slow-wave sleep. If you get less than seven hours a night, you will wind up with a shortage of human growth hormone. Any food that can help you sleep better is vital for hormone production. Getting eight hours of sleep is crucial for optimum HGH secretion. Pineapple is a top contender for HGH honors as it helps you fall asleep by increasing serotonin and melatonin production.

Other foods that naturally increase human growth hormone can have an impact during the day. Coconut oil can raise HGH levels for up to 4 hours. Consuming this in the morning and late afternoon can keep HGH production amped throughout the day.

Any food containing L-glutamine and L-arginine will be a hormonal powerhouse. Goji berries and grass-fed beef take the honors here.

Of the top 10 foods that increase human growth hormone, consuming organic, unpasteurized plain yogurt after dinner boosts HGH levels into the evening. Other beneficial foods that did not make the top 10 list include:

Raisins L-arginine

Raspberries melatonin

Parmesan cheese growth-inducing peptides

Raw fish omega-3 fatty acids

Gelatin L-glutamine

Algae spirulina and chlorella

Beets boost nitric oxide and testosterone

Lemons helps balance PH levels with alkaline to increase HGH

Will Eating Certain Foods Reverse Human Growth Hormone Deficiency?

Once you have HGH deficiency, you may feel as though you are fighting an uphill battle. Using food for increasing human growth hormone works best before you have a deficiency. That does not mean it will not help once you already have symptoms of decline. It will just take much longer for you to notice a significant difference.

Why Men and Women Should Consider Taking HGH and Testosterone

Age-related declines in human growth hormone (HGH) and testosterone are associated with increased body fat and decreased bone mineral density and lean muscle mass. However, when ashwagandha testosterone and HGH are taken together, this combination therapy can help reduce body fat, increase lean muscle mass, and improve bone-mineral density for overall improved quality of life.

Hormone fluctuation is a natural occurrence throughout a persons life. For women, events that affect hormone production include genetics, puberty, menopause, perimenopause, environmental toxins, sleep, exercise, stress, aging, and nutrition.

Role of HGH and Testosterone

Testosterone plays an essential role in brain function, bone strength, and muscle mass and strength. Also, it helps contribute to higher energy levels, increased sex drive, and a general sense of overall well-being.

On the other hand, HGH helps regulate heart function, body fluids, body composition, sugar and fat metabolism, and muscle and bone growth. This hormone is produced by the bodys pituitary gland, which stimulates cell regeneration and tissue growth and maintenance.

Both HGH and testosterone are critical to maintaining heart function, tissue, bones, muscles, and other organ function. Low levels of HGH and testosterone in the body could lead to the following signs and symptoms:

HGH and Testosterone Therapy

HGH and testosterone therapy will give you a toned, sexy body, tighter skin, shinier hair, and stronger nails, as well as the following benefits:

Conclusion

Now, you already have a better understanding of the role of HGH and testosterone in attaining overall health and well-being. While you can consume foods that can help increase HGH and testosterone, combination therapy can also help benefit from these two amazing hormones.

Visit link:

10 Foods That Increase Human Growth Hormone - Medicalopedia

Endocrine disruptor – Wikipedia

Chemicals that can interfere with endocrine or hormonal systems

Endocrine disruptors, sometimes also referred to as hormonally active agents,[1] endocrine disrupting chemicals,[2] or endocrine disrupting compounds[3] are chemicals that can interfere with endocrine (or hormonal) systems. These disruptions can cause cancerous tumors, birth defects, and other developmental disorders.[4] Found in many household and industrial products, endocrine disruptors "interfere with the synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body that are responsible for development, behavior, fertility, and maintenance of homeostasis (normal cell metabolism)."[5]

Any system in the body controlled by hormones can be derailed by hormone disruptors. Specifically, endocrine disruptors may be associated with the development of learning disabilities, severe attention deficit disorder, cognitive and brain development problems.[6][7][8][9]

There has been controversy over endocrine disruptors, with some groups calling for swift action by regulators to remove them from the market, and regulators and other scientists calling for further study.[10] Some endocrine disruptors have been identified and removed from the market (for example, a drug called diethylstilbestrol), but it is uncertain whether some endocrine disruptors on the market actually harm humans and wildlife at the doses to which wildlife and humans are exposed. Additionally, a key scientific paper, published in 1996 in the journal Science, which helped launch the movement of those opposed to endocrine disruptors, was retracted and its author found to have committed scientific misconduct.[11]

Studies in cells and laboratory animals have shown that EDCs can cause adverse biological effects in animals, and low-level exposures may also cause similar effects in human beings.[12]EDCs in the environment may also be related to reproductive and infertility problems in wildlife and bans and restrictions on their use has been associated with a reduction in health problems and the recovery of some wildlife populations.

The term endocrine disruptor was coined in 1991 at the Wingspread Conference Center in Wisconsin. One of the early papers on the phenomenon was by Theo Colborn in 1993.[13] In this paper, she stated that environmental chemicals disrupt the development of the endocrine system, and that effects of exposure during development are often permanent.Although the endocrine disruption has been disputed by some,[14] work sessions from 1992 to 1999 have generated consensus statements from scientists regarding the hazard from endocrine disruptors, particularly in wildlife and also in humans.[15][16][17][18][19]

The Endocrine Society released a scientific statement outlining mechanisms and effects of endocrine disruptors on "male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology," and showing how experimental and epidemiological studies converge with human clinical observations "to implicate endocrine disruptive chemicals (EDCs) as a significant concern to public health." The statement noted that it is difficult to show that endocrine disruptors cause human diseases, and it recommended that the precautionary principle should be followed.[20] A concurrent statement expresses policy concerns.[21]

Endocrine disrupting compounds encompass a variety of chemical classes, including drugs, pesticides, compounds used in the plastics industry and in consumer products, industrial by-products and pollutants, and even some naturally produced botanical chemicals. Some are pervasive and widely dispersed in the environment and may bioaccumulate. Some are persistent organic pollutants (POPs), and can be transported long distances across national boundaries and have been found in virtually all regions of the world, and may even concentrate near the North Pole, due to weather patterns and cold conditions.[22] Others are rapidly degraded in the environment or human body or may be present for only short periods of time.[23] Health effects attributed to endocrine disrupting compounds include a range of reproductive problems (reduced fertility, male and female reproductive tract abnormalities, and skewed male/female sex ratios, loss of fetus, menstrual problems[24]); changes in hormone levels; early puberty; brain and behavior problems; impaired immune functions; and various cancers.[25]

One example of the consequences of the exposure of developing animals, including humans, to hormonally active agents is the case of the drug diethylstilbestrol (DES), a nonsteroidal estrogen and not an environmental pollutant. Prior to its ban in the early 1970s, doctors prescribed DES to as many as five million pregnant women to block spontaneous abortion, an off-label use of this medication prior to 1947. It was discovered after the children went through puberty that DES affected the development of the reproductive system and caused vaginal cancer. The relevance of the DES saga to the risks of exposure to endocrine disruptors is questionable, as the doses involved are much higher in these individuals than in those due to environmental exposures.[26]

Aquatic life subjected to endocrine disruptors in an urban effluent have experienced decreased levels of serotonin and increased feminization.[27]

In 2013 the WHO and the United Nations Environment Programme released a study, the most comprehensive report on EDCs to date, calling for more research to fully understand the associations between EDCs and the risks to health of human and animal life. The team pointed to wide gaps in knowledge and called for more research to obtain a fuller picture of the health and environmental impacts of endocrine disruptors. To improve global knowledge the team has recommended:

Endocrine systems are found in most varieties of animals. The endocrine system consists of glands that secrete hormones, and receptors that detect and react to the hormones.

Hormones travel throughout the body and act as chemical messengers. Hormones interface with cells that contain matching receptors in or on their surfaces. The hormone binds with the receptor, much like a key would fit into a lock. The endocrine system regulates adjustments through slower internal processes, using hormones as messengers. The endocrine system secretes hormones in response to environmental stimuli and to orchestrate developmental and reproductive changes. The adjustments brought on by the endocrine system are biochemical, changing the cell's internal and external chemistry to bring about a long term change in the body. These systems work together to maintain the proper functioning of the body through its entire life cycle. Sex steroids such as estrogens and androgens, as well as thyroid hormones, are subject to feedback regulation, which tends to limit the sensitivity of these glands.

Hormones work at very small doses (part per billion ranges). Endocrine disruption can thereby also occur from low-dose exposure to exogenous hormones or hormonally active chemicals such as bisphenol A. These chemical can bind to receptors for other hormonally mediated processes.[29] Furthermore, since endogenous hormones are already present in the body in biologically active concentrations, additional exposure to relatively small amounts of exogenous hormonally active substances can disrupt the proper functioning of the body's endocrine system. Thus, an endocrine disruptor can elicit adverse effects at much lower doses than a toxicity, acting through a different mechanism.

The timing of exposure is also critical. Most critical stages of development occur in utero, where the fertilized egg divides, rapidly developing every structure of a fully formed baby, including much of the wiring in the brain. Interfering with the hormonal communication in utero can have profound effects both structurally and toward brain development. Depending on the stage of reproductive development, interference with hormonal signaling can result in irreversible effects not seen in adults exposed to the same dose for the same length of time.[30][31][32] Experiments with animals have identified critical developmental time points in utero and days after birth when exposure to chemicals that interfere with or mimic hormones have adverse effects that persist into adulthood.[31][33][34][35] Disruption of thyroid function early in development may be the cause of abnormal sexual development in both males[36] and females[37] early motor development impairment,[38] and learning disabilities.[39]

There are studies of cell cultures, laboratory animals, wildlife, and accidentally exposed humans that show that environmental chemicals cause a wide range of reproductive, developmental, growth, and behavior effects, and so while "endocrine disruption in humans by pollutant chemicals remains largely undemonstrated, the underlying science is sound and the potential for such effects is real."[40] While compounds that produce estrogenic, androgenic, antiandrogenic, and antithyroid actions have been studied, less is known about interactions with other hormones.

The interrelationships between exposures to chemicals and health effects are rather complex. It is hard to definitively link a particular chemical with a specific health effect, and exposed adults may not show any ill effects. But, fetuses and embryos, whose growth and development are highly controlled by the endocrine system, are more vulnerable to exposure and may develop overt or subtle lifelong health or reproductive abnormalities.[41] Prebirth exposure, in some cases, can lead to permanent alterations and adult diseases.[42]

Some in the scientific community are concerned that exposure to endocrine disruptors in the womb or early in life may be associated with neurodevelopmental disorders including reduced IQ, ADHD, and autism.[43] Certain cancers and uterine abnormalities in women are associated with exposure to diethylstilbestrol (DES) in the womb due to DES used as a medical treatment.

In another case, phthalates in pregnant women's urine was linked to subtle, but specific, genital changes in their male infantsa shorter, more female-like anogenital distance and associated incomplete descent of testes and a smaller scrotum and penis.[44] The science behind this study has been questioned by phthalate industry consultants.[45] As of June 2008, there are only five studies of anogenital distance in humans,[46] and one researcher has stated "Whether AGD measures in humans relate to clinically important outcomes, however, remains to be determined, as does its utility as a measure of androgen action in epidemiologic studies."[47]

While the fact that there are chemical differences between endocrine disruptors and endogenous hormones have sometimes been cited as an argument for endocrine disruptors affecting only some (not all) of the traits that are affected by hormones, toxicology research shows that many of the effects of endocrine disruptors target the aspects of hormone effects that make one hormone regulate the production and/or degradation of the body's own hormones. These regulation effects are intertwined so that a hormone that is level affected by another hormone in turn affects the levels of multiple other hormones produced by the body itself, leaving no endogenous hormones or traits affected by them unaffected by endocrine disruptors.[48][49] Endocrine disruptors have the potential to mimic or antagonize natural hormones, these chemicals can exert their effects by acting through interaction with nuclear receptors, the aryl hydrocarbon receptor or membrane bound receptors.[50][51]

Most toxicants, including endocrine disruptors, have been claimed to follow a U-shaped dose-response curve.[52] This means that very low and very high levels have more effects than mid-level exposure to a toxicant.[53]Endocrine disrupting effects have been noted in animals exposed to environmentally relevant levels of some chemicals. For example, a common flame retardant, BDE-47, affects the reproductive system and thyroid gland of female rats in doses of the order of those to which humans are exposed.[54]Low concentrations of endocrine disruptors can also have synergistic effects in amphibians, but it is not clear that this is an effect mediated through the endocrine system.[55]

Critics have argued that data suggest that the amounts of chemicals in the environment are too low to cause an effect. A consensus statement by the Learning and Developmental Disabilities Initiative argued that "The very low-dose effects of endocrine disruptors cannot be predicted from high-dose studies, which contradicts the standard 'dose makes the poison' rule of toxicology. Nontraditional dose-response curves are referred to as nonmonotonic dose response curves."[43]

The dosage objection could also be overcome if low concentrations of different endocrine disruptors are synergistic.[56] This paper was published in Science in June 1996, and was one reason for the passage of the Food Quality Protection Act of 1996.[57] The results could not be confirmed with the same and alternative methodologies,[58] and the original paper was retracted,[59] with Arnold found to have committed scientific misconduct by the United States Office of Research Integrity.[11]

It has been claimed that tamoxifen and some phthalates have fundamentally different (and harmful) effects on the body at low doses than at high doses.[60]

Food is a major mechanism by which people are exposed to pollutants. Diet is thought to account for up to 90% of a person's PCB and DDT body burden.[61] In a study of 32 different common food products from three grocery stores in Dallas, fish and other animal products were found to be contaminated with PBDE.[62] Since these compounds are fat-soluble, it is likely they are accumulating from the environment in the fatty tissue of animals eaten by humans. Some suspect fish consumption is a major source of many environmental contaminants. Indeed, both wild and farmed salmon from all over the world have been shown to contain a variety of man-made organic compounds.[63]

With the increase in household products containing pollutants and the decrease in the quality of building ventilation, indoor air has become a significant source of pollutant exposure.[64] Residents living in houses with wood floors treated in the 1960s with PCB-based wood finish have a much higher body burden than the general population.[65] A study of indoor house dust and dryer lint of 16 homes found high levels of all 22 different PBDE congeners tested for in all samples.[66] Recent studies suggest that contaminated house dust, not food, may be the major source of PBDE in our bodies.[67][68] One study estimated that ingestion of house dust accounts for up to 82% of humans' PBDE body burden.[69]

It has been shown that contaminated house dust is a primary source of lead in young children's bodies.[70] It may be that babies and toddlers ingest more contaminated house dust than the adults they live with, and therefore have much higher levels of pollutants in their systems.

Consumer goods are another potential source of exposure to endocrine disruptors. An analysis of the composition of 42 household cleaning and personal care products versus 43 "chemical-free" products has been performed. The products contained 55 different chemical compounds: 50 were found in the 42 conventional samples representing 170 product types, while 41 were detected in 43 "chemical-free" samples representing 39 product types. Parabens, a class of chemicals that has been associated with reproductive-tract issues, were detected in seven of the "chemical-free" products, including three sunscreens that did not list parabens on the label. Vinyl products such as shower curtains were found to contain more than 10% by weight of the compound DEHP, which when present in dust has been associated with asthma and wheezing in children. The risk of exposure to EDCs increases as products, both conventional and "chemical-free", are used in combination. "If a consumer used the alternative surface cleaner, tub and tile cleaner, laundry detergent, bar soap, shampoo and conditioner, facial cleanser and lotion, and toothpaste [he or she] would potentially be exposed to at least 19 compounds: 2 parabens, 3 phthalates, MEA, DEA, 5 alkylphenols, and 7 fragrances."[71]

An analysis of the endocrine-disrupting chemicals in Old Order Mennonite women in mid-pregnancy determined that they have much lower levels in their systems than the general population. Mennonites eat mostly fresh, unprocessed foods, farm without pesticides, and use few or no cosmetics or personal care products. One woman who had reported using hairspray and perfume had high levels of monoethyl phthalate, while the other women all had levels below detection. Three women who reported being in a car or truck within 48 hours of providing a urine sample had higher levels of diethylhexyl phthalate, which is found in polyvinyl chloride and is used in car interiors.[72]

Additives added to plastics during manufacturing may leach into the environment after the plastic item is discarded; additives in microplastics in the ocean leach into ocean water and in plastics in landfills may escape and leach into the soil and then into groundwater.[73]

All people are exposed to chemicals with estrogenic effects in their everyday life, because endocrine disrupting chemicals are found in low doses in thousands of products. Chemicals commonly detected in people include DDT, polychlorinated biphenyls (PCBs), bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), and a variety of phthalates.[74] In fact, almost all plastic products, including those advertised as "BPA-free", have been found to leach endocrine-disrupting chemicals.[75] In a 2011, study it was found that some "BPA-free" products released more endocrine active chemicals than the BPA-containing products.[76][77] Other forms of endocrine disruptors are phytoestrogens (plant hormones).[78]

Xenoestrogens are a type of xenohormone that imitates estrogen. Synthetic xenoestrogens include widely used industrial compounds, such as PCBs, BPA and phthalates, which have estrogenic effects on a living organism.

Alkylphenols are xenoestrogens.[79] The European Union has implemented sales and use restrictions on certain applications in which nonylphenols are used because of their alleged "toxicity, persistence, and the liability to bioaccumulate" but the United States Environmental Protections Agency (EPA) has taken a slower approach to make sure that action is based on "sound science".[80]

The long-chain alkylphenols are used extensively as precursors to the detergents, as additives for fuels and lubricants, polymers, and as components in phenolic resins. These compounds are also used as building block chemicals that are also used in making fragrances, thermoplastic elastomers, antioxidants, oil field chemicals and fire retardant materials. Through the downstream use in making alkylphenolic resins, alkylphenols are also found in tires, adhesives, coatings, carbonless copy paper and high performance rubber products. They have been used in industry for over 40 years.

Certain alkylphenols are degradation products from nonionic detergents. Nonylphenol is considered to be a low-level endocrine disruptor owing to its tendency to mimic estrogen.[81][82]

Bisphenol A is commonly found in plastic bottles, plastic food containers, dental materials, and the linings of metal food and infant formula cans. Another exposure comes from receipt paper commonly used at grocery stores and restaurants, because today the paper is commonly coated with a BPA containing clay for printing purposes.[83]

BPA is a known endocrine disruptor, and numerous studies have found that laboratory animals exposed to low levels of it have elevated rates of diabetes, mammary and prostate cancers, decreased sperm count, reproductive problems, early puberty, obesity, and neurological problems.[84][85][86][87] Early developmental stages appear to be the period of greatest sensitivity to its effects, and some studies have linked prenatal exposure to later physical and neurological difficulties.[88] Regulatory bodies have determined safety levels for humans, but those safety levels are currently being questioned or are under review as a result of new scientific studies.[89][90] A 2011 cross-sectional study that investigated the number of chemicals pregnant women are exposed to in the U.S. found BPA in 96% of women.[91]In 2010 the World Health Organization expert panel recommended no new regulations limiting or banning the use of bisphenol A, stating that "initiation of public health measures would be premature."[92]

In August 2008, the U.S. FDA issued a draft reassessment, reconfirming their initial opinion that, based on scientific evidence, it is safe.[93] However, in October 2008, FDA's advisory Science Board concluded that the Agency's assessment was "flawed" and had not proven the chemical to be safe for formula-fed infants.[94] In January 2010, the FDA issued a report indicating that, due to findings of recent studies that used novel approaches in testing for subtle effects, both the National Toxicology Program at the National Institutes of Health as well as the FDA have some level of concern regarding the possible effects of BPA on the brain and behavior of fetuses, infants and younger children.[95] In 2012 the FDA did ban the use of BPA in baby bottles, however the Environmental Working Group called the ban "purely cosmetic". In a statement they said, "If the agency truly wants to prevent people from being exposed to this toxic chemical associated with a variety of serious and chronic conditions it should ban its use in cans of infant formula, food and beverages." The Natural Resources Defense Council called the move inadequate saying, the FDA needs to ban BPA from all food packaging.[96] In a statement a FDA spokesman said the agency's action was not based on safety concerns and that "the agency continues to support the safety of BPA for use in products that hold food."[97]

A program initiated by NIEHS, NTP, and the U.S. Food and Drug Administration (named CLARITY-BPA) found no effect of chronic exposure to BPA on rats[98] and the FDA considers currently authorized uses of BPA to be safe for consumers.[99]

Bisphenol S and Bisphenol F are analogs of bisphenol A. They are commonly found in thermal receipts, plastics, and household dust.

Traces of BPS have also been found in personal care products.[100] It is more presently being used because of the ban of BPA. BPS is used in place of BPA in "BPA free" items. However BPS and BPF have been shown to be as much of an endocrine disruptor as BPA.[101][102]

Dichlorodiphenyltrichloroethane (DDT) was first used as a pesticide against Colorado potato beetles on crops beginning in 1936.[103] An increase in the incidence of malaria, epidemic typhus, dysentery, and typhoid fever led to its use against the mosquitoes, lice, and houseflies that carried these diseases. Before World War II, pyrethrum, an extract of a flower from Japan, had been used to control these insects and the diseases they can spread. During World War II, Japan stopped exporting pyrethrum, forcing the search for an alternative. Fearing an epidemic outbreak of typhus, every British and American soldier was issued DDT, who used it to routinely dust beds, tents, and barracks all over the world.

DDT was approved for general, non-military use after the war ended.[103] It became used worldwide to increase monoculture crop yields that were threatened by pest infestation, and to reduce the spread of malaria which had a high mortality rate in many parts of the world. Its use for agricultural purposes has since been prohibited by national legislation of most countries, while its use as a control against malaria vectors is permitted, as specifically stated by the Stockholm Convention on Persistent Organic Pollutants.[104]

As early as 1946, the harmful effects of DDT on bird, beneficial insects, fish, and marine invertebrates were seen in the environment. The most infamous example of these effects were seen in the eggshells of large predatory birds, which did not develop to be thick enough to support the adult bird sitting on them.[105] Further studies found DDT in high concentrations in carnivores all over the world, the result of biomagnification through the food chain.[106] Twenty years after its widespread use, DDT was found trapped in ice samples taken from Antarctic snow, suggesting wind and water are another means of environmental transport.[107] Recent studies show the historical record of DDT deposition on remote glaciers in the Himalayas.[108]

More than sixty years ago when biologists began to study the effects of DDT on laboratory animals, it was discovered that DDT interfered with reproductive development.[109][110] Recent studies suggest DDT may inhibit the proper development of female reproductive organs that adversely affects reproduction into maturity.[111] Additional studies suggest that a marked decrease in fertility in adult males may be due to DDT exposure.[112] Most recently, it has been suggested that exposure to DDT in utero can increase a child's risk of childhood obesity.[113] DDT is still used as anti-malarial insecticide in Africa and parts of Southeast Asia in limited quantities.

Polychlorinated biphenyls (PCBs) are a class of chlorinated compounds used as industrial coolants and lubricants. PCBs are created by heating benzene, a byproduct of gasoline refining, with chlorine.[114] They were first manufactured commercially by the Swann Chemical Company in 1927.[115] In 1933, the health effects of direct PCB exposure was seen in those who worked with the chemicals at the manufacturing facility in Alabama. In 1935, Monsanto acquired the company, taking over US production and licensing PCB manufacturing technology internationally.

General Electric was one of the largest US companies to incorporate PCBs into manufactured equipment.[115] Between 1952 and 1977, the New York GE plant had dumped more than 500,000 pounds of PCB waste into the Hudson River. PCBs were first discovered in the environment far from its industrial use by scientists in Sweden studying DDT.[116]

The effects of acute exposure to PCBs were well known within the companies who used Monsanto's PCB formulation who saw the effects on their workers who came into contact with it regularly. Direct skin contact results in a severe acne-like condition called chloracne.[117] Exposure increases the risk of skin cancer,[118] liver cancer,[119] and brain cancer.[118][120] Monsanto tried for years to downplay the health problems related to PCB exposure in order to continue sales.[121]

The detrimental health effects of PCB exposure to humans became undeniable when two separate incidents of contaminated cooking oil poisoned thousands of residents in Japan (Yush disease, 1968) and Taiwan (Yu-cheng disease, 1979),[122] leading to a worldwide ban on PCB use in 1977. Recent studies show the endocrine interference of certain PCB congeners is toxic to the liver and thyroid,[123] increases childhood obesity in children exposed prenatally,[113] and may increase the risk of developing diabetes.[124][125]

PCBs in the environment may also be related to reproductive and infertility problems in wildlife. In Alaska, it is thought that they may contribute to reproductive defects, infertility and antler malformation in some deer populations. Declines in the populations of otters and sea lions may also be partially due to their exposure to PCBs, the insecticide DDT, other persistent organic pollutants. Bans and restrictions on the use of EDCs have been associated with a reduction in health problems and the recovery of some wildlife populations.[126]

Polybrominated diphenyl ethers (PBDEs) are a class of compounds found in flame retardants used in plastic cases of televisions and computers, electronics, carpets, lighting, bedding, clothing, car components, foam cushions and other textiles. Potential health concern: PBDEs are structurally very similar to Polychlorinated biphenyls (PCBs), and have similar neurotoxic effects.[127] Research has correlated halogenated hydrocarbons, such as PCBs, with neurotoxicity.[123] PBDEs are similar in chemical structure to PCBs, and it has been suggested that PBDEs act by the same mechanism as PCBs.[123]

In the 1930s and 1940s, the plastics industry developed technologies to create a variety of plastics with broad applications.[128] Once World War II began, the US military used these new plastic materials to improve weapons, protect equipment, and to replace heavy components in aircraft and vehicles.[128] After WWII, manufacturers saw the potential plastics could have in many industries, and plastics were incorporated into new consumer product designs. Plastics began to replace wood and metal in existing products as well, and today plastics are the most widely used manufacturing materials.[128]

By the 1960s, all homes were wired with electricity and had numerous electrical appliances. Cotton had been the dominant textile used to produce home furnishings,[129] but now home furnishings were composed of mostly synthetic materials. More than 500 billion cigarettes were consumed each year in the 1960s, as compared to less than 3 billion per year in the beginning of the twentieth century.[130] When combined with high density living, the potential for home fires was higher in the 1960s than it had ever been in the US. By the late 1970s, approximately 6000 people in the US died each year in home fires.[131]

In 1972, in response to this situation, the National Commission on Fire Prevention and Control was created to study the fire problem in the US. In 1973 they published their findings in America Burning, a 192-page report[132] that made recommendations to increase fire prevention. Most of the recommendations dealt with fire prevention education and improved building engineering, such as the installation of fire sprinklers and smoke detectors. The Commission expected that with the recommendations, a 5% reduction in fire losses could be expected each year, halving the annual losses within 14 years.

Historically, treatments with alum and borax were used to reduce the flammability of fabric and wood, as far back as Roman times.[133] Since it is a non-absorbent material once created, flame retardant chemicals are added to plastic during the polymerization reaction when it is formed. Organic compounds based on halogens like bromine and chlorine are used as the flame retardant additive in plastics, and in fabric based textiles as well.[133] The widespread use of brominated flame retardants may be due to the push from Great Lakes Chemical Corporation (GLCC) to profit from its huge investment in bromine.[134] In 1992, the world market consumed approximately 150,000 tonnes of bromine-based flame retardants, and GLCC produced 30% of the world supply.[133]

PBDEs have the potential to disrupt thyroid hormone balance and contribute to a variety of neurological and developmental deficits, including low intelligence and learning disabilities.[135][136] Many of the most common PBDE's were banned in the European Union in 2006.[137] Studies with rodents have suggested that even brief exposure to PBDEs can cause developmental and behavior problems in juvenile rodents[38][138] and exposure interferes with proper thyroid hormone regulation.[139]

Phthalates are found in some soft toys, flooring, medical equipment, cosmetics and air fresheners. They are of potential health concern because they are known to disrupt the endocrine system of animals, and some research has implicated them in the rise of birth defects of the male reproductive system.[44][140][141]

Although an expert panel has concluded that there is "insufficient evidence" that they can harm the reproductive system of infants,[142] California,[143][144] Washington state,[145] and Europe have banned them from toys. One phthalate, bis(2-ethylhexyl) phthalate (DEHP), used in medical tubing, catheters and blood bags, may harm sexual development in male infants.[140] In 2002, the Food and Drug Administration released a public report which cautioned against exposing male babies to DEHP. Although there are no direct human studies the FDA report states: "Exposure to DEHP has produced a range of adverse effects in laboratory animals, but of greatest concern are effects on the development of the male reproductive system and production of normal sperm in young animals. In view of the available animal data, precautions should be taken to limit the exposure of the developing male to DEHP".[146] Similarly, phthalates may play a causal role in disrupting masculine neurological development when exposed prenatally.[147]

Dibutyl phthalate (DBP) has also disrupted insulin and glucagon signaling in animal models.[148]

PFOA exerts hormonal effects including alteration of thyroid hormone levels. Blood serum levels of PFOA were associated with an increased time to pregnancyor "infertility"in a 2009 study. PFOA exposure is associated with decreased semen quality. PFOA appeared to act as an endocrine disruptor by a potential mechanism on breast maturation in young girls. A C8 Science Panel status report noted an association between exposure in girls and a later onset of puberty.

Some other examples of putative EDCs are polychlorinated dibenzo-dioxins (PCDDs) and -furans (PCDFs), polycyclic aromatic hydrocarbons (PAHs), phenol derivatives and a number of pesticides (most prominent being organochlorine insecticides like endosulfan, kepone (chlordecone) and DDT and its derivatives, the herbicide atrazine, and the fungicide vinclozolin), the contraceptive 17-alpha ethinylestradiol, as well as naturally occurring phytoestrogens such as genistein and mycoestrogens such as zearalenone.

The molting in crustaceans is an endocrine-controlled process. In the marine penaeid shrimp Litopenaeus vannamei, exposure to endosulfan resulted increased susceptibility to acute toxicity and increased mortalities in the postmolt stage of the shrimp.[149]

Many sunscreens contain oxybenzone, a chemical blocker that provides broad-spectrum UV coverage, yet is subject to a lot of controversy due its potential estrogenic effect in humans.[150]

Tributyltin (TBT) are organotin compounds. For 40 years TBT was used as a biocide in anti-fouling paint, commonly known as bottom paint. TBT has been shown to impact invertebrate and vertebrate development, disrupting the endocrine system, resulting in masculinization, lower survival rates, as well as many health problems in mammals.

Since being banned, the average human body burdens of DDT and PCB have been declining.[61][151][152] Since their ban in 1972, the PCB body burden in 2009 is one-hundredth of what it was in the early 1980s. On the other hand, monitoring programs of European breast milk samples have shown that PBDE levels are increasing.[61][152] An analysis of PBDE content in breast milk samples from Europe, Canada, and the US shows that levels are 40 times higher for North American women than for Swedish women, and that levels in North America are doubling every two to six years.[153][154]

It has been discussed that the long-term slow decline in average body temperature observed since the beginning of the industrial revolution[155] may result from disrupted thyroid hormone signalling.[156]

Because endocrine disruptors affect complex metabolic, reproductive, and neuroendocrine systems, they cannot be modeled in in vitro cell based assay. Consequently, animal models are important for access the risk of endocrine disrupting chemicals.[157]

There are multiple lines of genetically engineered mice used for lab studies, in this case the lines can be used as population-based genetic foundations. For instance, there is a population that is named Multi-parent and can be a Collaborative Cross (CC) or Diversity Outbred (DO). These mice while both from the same eight founder strains, have distinct differences.[158][159][160]

The eight founder strains, combine strains that are wild-derived (with high genetic diversity) and historically significant biomedical research bred strains. Each genetically differential line is important in EDCs response and also almost all biological processes and traits.[161]

The CC population consists of 83 inbred mouse strains that over many generations in labs came from the 8 founder strains. These inbred mice have recombinant genomes that are developed to ensure every strain is equally related, this eradicates population structure and can result in false positives with qualitative trait locus (QTL) mapping.

While DO mice have the identical alleles to the CC mice population. There are two major differences in these mice; 1) every individual is unique allowing for hundreds of individuals to be applied in one mapping study. Making DO mice an extremely useful tool for determining genetic relationships. 2) The catch is that DO individuals cannot be reproduced.

These rodents mainly mice have been bred by inserting other genes from another organism to make transgenic lines (thousands of lines) of rodents. The most recent tool used to do this is CRISPR/Cas9 which allows this process to be done more efficiently.[162]

Genes may be manipulated in a particular cell populations if done under the correct conditions.[163] For Endocrine disrupting chemical (EDC) research these rodents have become an important tool to the point where they can produce humanized mouse models.[164][165] Additionally scientists use gene knockout lines of mice in order to study how certain mechanisms work when impacted by EDC's.[164][165][166][167] Transgenic rodents are an important tool for studies involving the mechanisms that are impacted by EDC but take a long time to produce and are expensive. Additionally, the genes aimed at for knockout are not always successfully targeted resulting in incomplete knockout of a gene or off-target expression.

Experiments (gene by environment) with these relatively new rodent models may, be able to discover if there are mechanisms that EDCs could impact in the social decline in autism spectrum disorder (ASD) and other behavioral disorders.[168][169] This is because prairie and pine voles are socially monogamous making them a better model for human social behaviors and development in relation to EDCs.[170][171][172][168][173] Additionally the prairie vole genome has been sequenced making it feasible to do the experiments mentioned above.[168][169] These voles can be compared to montane and meadow voles who are socially promiscuous and solitary, when looking at how different species have various forms of development and social brain structure.[172][168][173] Both monogamous and promiscuous mice species have been used in these types of experiments, for more information studies[174] can expand on this topic.[175][176][174][177] More complex models that have systems that are as close as possible to humans are being looked at. Looking back at more common rodent models for instance the common ASD mouse are helpful but do not fully encompass what a model of the human social behaviors needs to. But these rodents will always just be models and this is important to keep in mind.[170][171]

The endocrine systems between mammals and fish are similar; because of this, zebrafish (Danio rerio) are a popular lab choice.[178] Zebrafish work well as a model organism, part of which can be attributed to the fact that researchers are able to study them starting from the embryo, as the embryo is nearly transparent.[178] Additionally, zebrafish have DNA sex markers, this allows the biologists to individually assign sex to fish, this is particularly important when studying endocrine disruptors as the disruptors can affect how, among other things, the sex organs work, so if by chance there is sperm in the ovaries later on through the testing it can then be pinned to the chemical without the chance of it being a genetic abnormality since the sex was determined by the researcher. Besides zebrafish being readily available, and easy to study through their different life stages, they have hugely similar genes to humans70% of human genes have a zebrafish counterpart and even more fascinatingly 84% of disease genes in humans have a zebrafish counterpart.[178] Most importantly perhaps is the fact that the vast majority of endocrine disruptors end up in water ways,[178] and so it is important to know how these disruptors affect fish, which arguably have intrinsic value and just happen to be model organisms as well.

The zebrafish embryos are transparent, relatively small fish (larvae are less than a few millimeters in size).[179] This allows scientists to view the larvae (in vivo) without killing them to study how their organs develop in particular, neuro development and transport of presumed endocrine disrupting chemicals (EDC). Meaning how their development is impacted by certain chemicals. As a model, they have simple modes of endocrine disruption.[180] Along with homologous physiological, sensory, anatomical and signal-transduction mechanism similar to mammals.[181] Another helpful tool available to scientists is their recorded genome along with multiple transgenic lines accessible for breeding. Zebrafish and mammalian genomes when compared have prominent similarities with about 80% of human genes expressed in the fish. Additionally, this fish is also fairly inexpensive to breed and house in a lab partly due to their shorter life span and being able to house more of them, compared to mammalian models.[182][183][184][179]

Research on endocrine disruptors is challenged by five complexities requiring special trial designs and sophisticated study protocols:[185]

The multitude of possible endocrine disruptors are technically regulated in the United States by many laws, including: the Toxic Substances Control Act, the Food Quality Protection Act,[189] the Food, Drug and Cosmetic Act, the Clean Water Act, the Safe Drinking Water Act, and the Clean Air Act.

The Congress of the United States has improved the evaluation and regulation process of drugs and other chemicals. The Food Quality Protection Act of 1996 and the Safe Drinking Water Act of 1996 simultaneously provided the first legislative direction requiring the EPA to address endocrine disruption through establishment of a program for screening and testing of chemical substances.

In 1998, the EPA announced the Endocrine Disruptor Screening Program by establishment of a framework for priority setting, screening and testing more than 85,000 chemicals in commerce. While the Food Quality Protection Act only required the EPA to screen pesticides for potential to produce effects similar to estrogens in humans, it also gave the EPA the authority to screen other types of chemicals and endocrine effects.[189] Based on recommendations from an advisory panel, the agency expanded the screening program to include male hormones, the thyroid system, and effects on fish and other wildlife.[189] The basic concept behind the program is that prioritization will be based on existing information about chemical uses, production volume, structure-activity and toxicity. Screening is done by use of in vitro test systems (by examining, for instance, if an agent interacts with the estrogen receptor or the androgen receptor) and via the use of in animal models, such as development of tadpoles and uterine growth in prepubertal rodents. Full scale testing will examine effects not only in mammals (rats) but also in a number of other species (frogs, fish, birds and invertebrates). Since the theory involves the effects of these substances on a functioning system, animal testing is essential for scientific validity, but has been opposed by animal rights groups. Similarly, proof that these effects occur in humans would require human testing, and such testing also has opposition.

After failing to meet several deadlines to begin testing, the EPA finally announced that they were ready to begin the process of testing dozens of chemical entities that are suspected endocrine disruptors early in 2007, eleven years after the program was announced. When the final structure of the tests was announced there was objection to their design. Critics have charged that the entire process has been compromised by chemical company interference.[190] In 2005, the EPA appointed a panel of experts to conduct an open peer-review of the program and its orientation. Their results found that "the long-term goals and science questions in the EDC program are appropriate",[191] however this study was conducted over a year before the EPA announced the final structure of the screening program. The EPA is still finding it difficult to execute a credible and efficient endocrine testing program.[189]

As of 2016, the EPA had estrogen screening results for 1,800 chemicals.[189]

In 2013, a number of pesticides containing endocrine disrupting chemicals were in draft EU criteria to be banned. On 2 May, US TTIP negotiators insisted the EU drop the criteria. They stated that a risk-based approach should be taken on regulation. Later the same day Catherine Day wrote to Karl Falkenberg asking for the criteria to be removed.[192]

The European Commission had been to set criteria by December 2013 identifying endocrine disrupting chemicals (EDCs) in thousands of productsincluding disinfectants, pesticides and toiletriesthat have been linked to cancers, birth defects and development disorders in children. However, the body delayed the process, prompting Sweden to state that it would sue the commission in May 2014blaming chemical industry lobbying for the disruption.[193]

"This delay is due to the European chemical lobby, which put pressure again on different commissioners. Hormone disrupters are becoming a huge problem. In some places in Sweden we see double-sexed fish. We have scientific reports on how this affects fertility of young boys and girls, and other serious effects," Swedish Environment Minister Lena Ek told the AFP, noting that Denmark had also demanded action.[193]

In November 2014, the Copenhagen-based Nordic Council of Ministers released its own independent report that estimated the impact of environmental EDCs on male reproductive health, and the resulting cost to public health systems. It concluded that EDCs likely cost health systems across the EU anywhere from 59 million to 1.18 billion Euros a year, noting that even this represented only "a fraction of the endocrine related diseases".[194]

In 2020, the EU published their Chemicals Strategy for Sustainability which is concerned with a green transition of the chemical industry away from xenohormones and other hazardous chemicals.

There is evidence that once a pollutant is no longer in use, or once its use is heavily restricted, the human body burden of that pollutant declines. Through the efforts of several large-scale monitoring programs,[74][195] the most prevalent pollutants in the human population are fairly well known. The first step in reducing the body burden of these pollutants is eliminating or phasing out their production.

The second step toward lowering human body burden is awareness of and potentially labeling foods that are likely to contain high amounts of pollutants. This strategy has worked in the pastpregnant and nursing women are cautioned against eating seafood that is known to accumulate high levels of mercury. Ideally,[according to whom?] a certification process should be in place to routinely test animal products for POP concentrations. This would help the consumer identify which foods have the highest levels of pollutants.

The most challenging aspect[citation needed] of this problem is discovering how to eliminate these compounds from the environment and where to focus remediation efforts. Even pollutants no longer in production persist in the environment, and bio-accumulate in the food chain. An understanding of how these chemicals, once in the environment, move through ecosystems, is essential to designing ways to isolate and remove them. Working backwards through the food chain may help to identify areas to prioritize for remediation efforts. This may be extremely challenging for contaminated fish and marine mammals that have a large habitat and who consume fish from many different areas throughout their lives.

Many persistent organic compounds, PCB, DDT and PBDE included, accumulate in river and marine sediments. Several processes are currently being used by the EPA to clean up heavily polluted areas, as outlined in their Green Remediation program.[196]

One of the most interesting ways is the utilization of naturally occurring microbes that degrade PCB congeners to remediate contaminated areas.[197]

There are many success stories of cleanup efforts of large heavily contaminated Superfund sites. A 10-acre (40,000m2) landfill in Austin, Texas contaminated with illegally dumped VOCs was restored in a year to a wetland and educational park.[198]

A US uranium enrichment site that was contaminated with uranium and PCBs was cleaned up with high tech equipment used to find the pollutants within the soil.[199] The soil and water at a polluted wetlands site were cleaned of VOCs, PCBs and lead, native plants were installed as biological filters, and a community program was implemented to ensure ongoing monitoring of pollutant concentrations in the area.[200] These case studies are encouraging due to the short amount of time needed to remediate the site and the high level of success achieved.

Studies suggest that bisphenol A,[201] certain PCBs,[202] and phthalate compounds[203] are preferentially eliminated from the human body through sweat.

Human exposure may cause some health effects, such as lower IQ and adult obesity. These effects may lead to lost productivity, disability, or premature death in some people. One source estimated that, within the European Union, this economic effect might have about twice the economic impact as the effects caused by mercury and lead contamination.[204]

The socio-economic burden of endocrine disrupting chemicals (EDC)-associated health effects for the European Union was estimated based on currently available literature and considering the uncertainties with respect to causality with EDCs and corresponding health-related costs to be in the range of 46 billion to 288 billion per year.[205]

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Endocrine disruptor - Wikipedia

Insulin-like growth factor 1 – Wikipedia

Protein-coding gene in the species Homo sapiens

1B9G, 1GZR, 1GZY, 1GZZ, 1H02, 1H59, 1IMX, 1PMX, 1TGR, 1WQJ, 2DSR, 2GF1, 3GF1, 3LRI, 1BQT, 4XSS

Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults.

IGF-1 is a protein that in humans is encoded by the IGF1 gene.[5][6] IGF-1 consists of 70 amino acids in a single chain with three intramolecular disulfide bridges. IGF-1 has a molecular weight of 7,649 Daltons.[7] In dogs, an ancient mutation in IGF1 is the primary cause of the toy phenotype.[8]

IGF-1 is produced primarily by the liver. Production is stimulated by growth hormone (GH). Most of IGF-1 is bound to one of 6 binding proteins (IGF-BP). IGFBP-1 is regulated by insulin. IGF-1 is produced throughout life; the highest rates of IGF-1 production occur during the pubertal growth spurt.[9] The lowest levels occur in infancy and old age.[10][11]

A synthetic analog of IGF-1, mecasermin, is used in children for the treatment of growth failure.[12]

IGF-1 is produced primarily by the liver as an endocrine hormone as well as in target tissues in a paracrine/autocrine fashion. Production is stimulated by growth hormone (GH) and can be retarded by undernutrition,[9] growth hormone insensitivity, lack of growth hormone receptors, or failures of the downstream signaling pathway post GH receptor including SHP2 and STAT5B. Approximately 98% of IGF-1 is always bound to one of 6 binding proteins (IGF-BP). IGFBP-3, the most abundant protein, accounts for 80% of all IGF binding. IGF-1 binds to IGFBP-3 in a 1:1 molar ratio. IGFBP-1 is regulated by insulin.[13]

IGF-1 is produced throughout life. The highest rates of IGF-1 production occur during the pubertal growth spurt. The lowest levels occur in infancy and old age.[medical citation needed][14]

Protein intake increases IGF-1 levels in humans, independent of total calorie consumption.[15] Factors that are known to cause variation in the levels of growth hormone (GH) and IGF-1 in the circulation include: insulin levels, genetic make-up, the time of day, age, sex, exercise status, stress levels, nutrition level and body mass index (BMI), disease state, ethnicity, estrogen status and xenobiotic intake.[16]

IGF-1 is a primary mediator of the effects of growth hormone (GH). Growth hormone is made in the anterior pituitary gland, is released into the blood stream, and then stimulates the liver to produce IGF-1. IGF-1 then stimulates systemic body growth, and has growth-promoting effects on almost every cell in the body, especially skeletal muscle, cartilage, bone, liver, kidney, nerve, skin, hematopoietic, and lung cells. In addition to the insulin-like effects, IGF-1 can also regulate cellular DNA synthesis.[17]

IGF-1 binds to at least two cell surface receptor tyrosine kinases: the IGF-1 receptor (IGF1R), and the insulin receptor. Its primary action is mediated by binding to its specific receptor, IGF1R, which is present on the surface of many cell types in many tissues. Binding to the IGF1R initiates intracellular signaling. IGF-1 is one of the most potent natural activators of the AKT signaling pathway, a stimulator of cell growth and proliferation, and a potent inhibitor of programmed cell death .[18][19] The IGF-1 receptor seems to be the "physiologic" receptor because it binds IGF-1 with significantly higher affinity than insulin receptor does. IGF-1 activates the insulin receptor at approximately 0.1 times the potency of insulin. Part of this signaling may be via IGF1R/Insulin Receptor heterodimers (the reason for the confusion is that binding studies show that IGF1 binds the insulin receptor 100-fold less well than insulin, yet that does not correlate with the actual potency of IGF1 in vivo at inducing phosphorylation of the insulin receptor, and hypoglycemia).[medical citation needed]

IGF-1 binds and activates its own receptor, IGF-1R, through the cell surface expression of Receptor Tyrosine Kinase's (RTK's)[20] and further signal through multiple intracellular transduction cascades. IGF-1R is the critical role-playing inducer in modulating the metabolic effects of IGF-1 for cellular senescence and survival. At a localized target cell, IGF-1R elicits the mediation of paracrine activity. After its activation the initiation of intracellular signaling occurs inducing a magnitude of signaling pathways. An important mechanistic pathway involved in mediating a cascade affect a key pathway regulated by phosphatidylinositol-3 kinase (PI3K) and its downstream partner, mTOR (mammalian Target of Rapamycin).[20] Rapamycin binds with the enzyme FKBPP12 to inhibit the mTORC1 complex. mTORC2 remains unaffected and responds by up-regulating AKT, driving signals through the inhibited mTORC1. Phosphorylation of Eukaryotic translation initiation factor 4E (EIF4E) by mTOR suppresses the capacity of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) to inhibit EIF4E and slow metabolism.[21] A mutation in the signaling pathway PI3K-AKT-mTOR is a big factor in the formation of tumors found predominantly on skin, internal organs, and secondary lymph nodes (Kaposi sarcoma).[22] IGF-1R allows the activation of these signaling pathways and subsequently regulates the cellular longevity and metabolic re-uptake of biogenic substances. A therapeutic approach targeting towards the reduction of such tumor collections could be induced by ganitumab. Ganitumab is a monoclonal antibody (mAb) directed antagonistically against IGF-1R. Ganitumab binds to IGF-1R, preventing binding of IGF-1 and the subsequent triggering of the PI3K-mTOR signaling pathway; inhibition of this pro-survival pathway may result in the inhibition of tumor cell expansion and the induction of tumor cell apoptosis.[citation needed]

Insulin-like growth factor 1 has been shown to bind and interact with all seven IGF-1 binding proteins (IGFBPs): IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, IGFBP6, and IGFBP7.[medical citation needed]Some IGFBPs are inhibitory. For example, both IGFBP-2 and IGFBP-5 bind IGF-1 at a higher affinity than it binds its receptor. Therefore, increases in serum levels of these two IGFBPs result in a decrease in IGF-1 activity.[medical citation needed]

As a major growth factor, IGF-1 is responsible for stimulating growth of all cell types and causing significant metabolic effects.[23] One important metabolic effect of IGF-1 is its ability to signal cells that sufficient nutrients are available for cells to undergo hypertrophy and cell division.[24] These signals also enable IGF-1 to inhibit cell apoptosis and increase the production of cellular proteins.[24] IGF-1 receptors are ubiquitous, which allows for metabolic changes caused by IGF-1 to occur in all cell types.[23] IGF-1's metabolic effects are far-reaching and can coordinate protein, carbohydrate, and fat metabolism in a variety of different cell types.[23] The regulation of IGF-1's metabolic effects on target tissues is also coordinated with other hormones such as growth hormone and insulin.[25]

IGF-1 is closely related to a second protein called "IGF-2". IGF-2 also binds the IGF-1 receptor. However, IGF-2 alone binds a receptor called the "IGF-2 receptor" (also called the mannose-6 phosphate receptor). The insulin-like growth factor-II receptor (IGF2R) lacks signal transduction capacity, and its main role is to act as a sink for IGF-2 and make less IGF-2 available for binding with IGF-1R.As the name "insulin-like growth factor 1" implies, IGF-1 is structurally related to insulin, and is even capable of binding the insulin receptor, albeit at lower affinity than insulin.

A splice variant of IGF-1 sharing an identical mature region, but with a different E domain is known as mechano-growth factor (MGF).[26]

Rare diseases characterized by inability to make or respond to IGF-1 produce a distinctive type of growth failure. One such disorder, termed Laron dwarfism does not respond at all to growth hormone treatment due to a lack of GH receptors. The FDA has grouped these diseases into a disorder called severe primary IGF deficiency. Patients with severe primary IGFD typically present with normal to high GH levels, height below3 standard deviations (SD), and IGF-1 levels below 3SD. Severe primary IGFD includes patients with mutations in the GH receptor, post-receptor mutations or IGF mutations, as previously described. As a result, these patients cannot be expected to respond to GH treatment.

People with Laron syndrome have very low rates of cancer and diabetes.[27] Notably people with untreated Laron syndrome also never develop acne.[28]

Acromegaly is a syndrome that results when the anterior pituitary gland produces excess growth hormone (GH). A number of disorders may increase the pituitary's GH output, although most commonly it involves a tumor called pituitary adenoma, derived from a distinct type of cell (somatotrophs). It leads to anatomical changes and metabolic dysfunction caused by both an elevated GH and elevated IGF-1 levels.[29] High level of IGF-1 in acromegaly is related to an increased risk of some cancers, particularly colon cancer and thyroid cancer.[30]

A mutation in the signaling pathway PI3K-AKT-mTOR is a factor in the formation of tumors found predominantly on skin, internal organs, and secondary lymph nodes (Kaposi sarcoma).[22]

IGF-1R allows the activation of these signaling pathways and subsequently regulates the cellular longevity and metabolic re-uptake of biogenic substances. A therapeutic approach targeting towards the reduction of such tumor collections could be induced by ganitumab. Ganitumab is a monoclonal antibody (mAb) directed antagonistically against IGF-1R. Ganitumab binds to IGF-1R, preventing binding of IGF-1 and the subsequent triggering of the PI3K-mTOR signaling pathway; inhibition of this pro-survival pathway may result in the inhibition of tumor cell expansion and the induction of tumor cell apoptosis.[citation needed]

IGF-1 levels can be measured in the blood in 10-1000ng/ml amounts.[31] As levels do not fluctuate greatly throughout the day for an individual person, IGF-1 is used by physicians as a screening test for growth hormone deficiency and excess in acromegaly and gigantism.

Interpretation of IGF-1 levels is complicated by the wide normal ranges, and marked variations by age, sex, and pubertal stage. Clinically significant conditions and changes may be masked by the wide normal ranges. Sequential measurement over time is often useful for the management of several types of pituitary disease, undernutrition, and growth problems.

Patients with severe primary insulin-like growth factor-1 deficiency (IGFD), called Laron syndrome, may be treated with either IGF-1 alone or in combination with IGFBP-3.[38] Mecasermin (brand name Increlex) is a synthetic analog of IGF-1 which is approved for the treatment of growth failure.[38] IGF-1 has been manufactured recombinantly on a large scale using both yeast and E. coli.

IGF-1 may have a beneficial effect on atherosclerosis and cardiovascular disease.[39] IGF-1 has also been shown to have an antidepressant effect in mouse models.[40]

Several companies have evaluated administering recombinant IGF-1 in clinical trials for type 1 diabetes, type 2 diabetes, amyotrophic lateral sclerosis,[41] severe burn injury and myotonic muscular dystrophy.

Results of clinical trials evaluating the efficacy of IGF-1 in type 1 diabetes and type 2 diabetes showed reduction in hemoglobin A1C levels and daily insulin consumption.[medical citation needed] However the sponsor discontinued the program due to an exacerbation of diabetic retinopathy,[42] coupled with a shift in corporate focus towards oncology.

Two clinical studies of IGF-1 for ALS were conducted and although one study demonstrated efficacy the second was equivocal,[medical citation needed] and the product was not submitted for approval to the FDA.

In the 1950s IGF-1 was called "sulfation factor" because it stimulated sulfation of cartilage in vitro,[43] and in the 1970s due to its effects it was termed "nonsuppressible insulin-like activity" (NSILA).

PDB gallery

1bqt: THREE-DIMENSIONAL STRUCTURE OF HUMAN INSULIN-LIKE GROWTH FACTOR-I (IGF-I) DETERMINED BY 1H-NMR AND DISTANCE GEOMETRY, 6 STRUCTURES

1gzr: HUMAN INSULIN-LIKE GROWTH FACTOR; ESRF DATA

1gzy: HUMAN INSULIN-LIKE GROWTH FACTOR; IN-HOUSE DATA

1gzz: HUMAN INSULIN-LIKE GROWTH FACTOR; HAMBURG DATA

1h02: HUMAN INSULIN-LIKE GROWTH FACTOR; SRS DARESBURY DATA

1h59: COMPLEX OF IGFBP-5 WITH IGF-I

1imx: 1.8 Angstrom crystal structure of IGF-1

1pmx: INSULIN-LIKE GROWTH FACTOR-I BOUND TO A PHAGE-DERIVED PEPTIDE

1wqj: Structural Basis for the Regulation of Insulin-Like Growth Factors (IGFs) by IGF Binding Proteins (IGFBPs)

2dsp: Structural Basis for the Inhibition of Insulin-like Growth Factors by IGF Binding Proteins

2dsq: Structural Basis for the Inhibition of Insulin-like Growth Factors by IGF Binding Proteins

2dsr: Structural Basis for the Inhibition of Insulin-like Growth Factors by IGF Binding Proteins

2gf1: SOLUTION STRUCTURE OF HUMAN INSULIN-LIKE GROWTH FACTOR 1: A NUCLEAR MAGNETIC RESONANCE AND RESTRAINED MOLECULAR DYNAMICS STUDY

3gf1: SOLUTION STRUCTURE OF HUMAN INSULIN-LIKE GROWTH FACTOR 1: A NUCLEAR MAGNETIC RESONANCE AND RESTRAINED MOLECULAR DYNAMICS STUDY

3lri: Solution structure and backbone dynamics of long-[Arg(3)]insulin-like growth factor-I

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Insulin-like growth factor 1 - Wikipedia

How can people increase HGH? – Medical News Today

Human growth hormone (HGH) is a hormone that promotes growth, muscle mass, and fat metabolism. It can be especially important during weight loss, injury recovery, and athletic training. People can try to increase their HGH naturally by changing their diet and lifestyle choices.

HGH, which is also known as somatotropin or growth hormone (GH), plays a vital role in body composition. The pituitary gland produces HGH and releases it into the bloodstream. The body regulates the production of HGH in response to stress, exercise, nutrition, sleep, and the growth hormone itself.

Natural HGH is important in growing children and teenagers. A lack of HGH production can lead to a condition known as growth hormone deficiency (GHD). This can lead to a slow growth rate, and reduced facial bone development.

Similarly, excess HGH production can lead to a condition known as acromegaly. This condition can result in a number of signs and symptoms, the most well known being large hands and feet.

This article will explore the benefits of HGH, as well as the risks. It will also look at some of the ways to naturally boost HGH within the body.

HGH has been associated with potential benefits such as:

HGH stimulates lipolysis, which is the breakdown of fatty acids in fat tissue. This can lead to weight loss.

An older study suggests that GH treatment may help decrease body fat in obesity and growth hormone deficiency. A 2015 review supports this, indicating that growth hormone-releasing hormone (GHRH) may be beneficial for people with obesity.

Research notes that GH can enhance muscle performance in sports and muscle function in older adults. GH may help to increase muscle mass and strength through anabolic effects, in a similar way to anabolic steroids.

However, it is worth noting that the World Anti-Doping Agency view HGH as a doping agent. They prohibit its use due to the positive effect it can have on athletic performance.

Evidence suggests that HGH may play a role in improving cognitive function. A 2013 review notes that GH may interact with specific receptors in the central nervous system, and may help improve memory and learning.

An older study suggests that GHRH may have a clinical use for treating skin wounds resulting from trauma, surgery, or disease. In particular, research suggests that HGH may help heal burn wounds and have a use in the rehabilitation process.

A 10-year study that involved 80 women between the ages of 5070 found that GH treatment was beneficial for bone health and fracture healing in postmenopausal women.

Currently, the Food and Drug Administration (FDA) have only approved the use of GH treatment for specific conditions, such as GHD. It is only available on prescription.

Some athletes have used HGH on a non-prescription basis to improve performance, but this carries the danger of excessive use, or incorrect dosing.

Long-term use of HGH can result in acromegaly. This can lead to a number of complications such as:

In addition to the above, some complications of GH replacement therapy due to excessive HGH may include:

As a person must administer HGH by injection, it runs the risk of blood clots, dose error, and allergic reaction at the site of injection. People should only use HGH under the supervision of a doctor.

The pituitary gland produces HGH in the body and releases it in bursts. The levels of HGH rise and fall regularly, and people can increase them naturally by:

A 2020 article notes that excessive body fat, including visceral and central fat, is associated with reduced HGH. This is consistent with a 2015 review, which states that increased visceral fat is associated with lower levels of GH.

This suggests that by reducing body fat, a person may be able to increase the natural secretion of HGH.

Exercise is a powerful stimulator of GH release. A 2015 study found that regular resistance exercise, such as the use of free weights and bodybuilding machines, led to increased secretion of HGH and another hormone known as insulin-like growth factor-1.

Athletes may try to abuse both of these hormones due to their anabolic properties that may help enhance physical ability.

A 2013 systematic review notes that intermittent fasting can substantially increase the levels of HGH. This may be due to the role HGH plays in breaking down fat, which the body may use for energy while fasting.

A reduction in a persons sugar intake may also lead to an increase in HGH levels.

The pancreas releases insulin in response to consuming sugar or other carbohydrates. Research suggests that insulin may dictate the secretion of GH. A consistent increase in insulin may inhibit the release of HGH, reducing the level of HGH in the body.

A 2020 study also notes that insulin and GH are counter-regulatory in terms of glucose and fat metabolism. In cases of obesity, when insulin is high and GH is low, the hormonal imbalance promotes further fat buildup, further reducing HGH.

This suggests that a reduction in sugar intake, which will lower the need for insulin, may help to increase levels of HGH.

People can also use supplements to increase the level of HGH in the body.

The amino acids arginine and glutamine have been associated with the release of HGH. A 2020 study suggests that oral supplementation with amino acids significantly increased HGH levels in healthy adults. Therefore, arginine and glutamine supplements may help to boost HGH.

Older research indicates that melatonin may stimulate the release of GH. Melatonin is a hormone that the pineal gland releases in the body. It releases higher quantities of melatonin during the night and signals the need for sleep.

However, it is advisable for a person to speak with their doctor before taking supplements or significantly changing their diet.

Research notes that HGH levels increase during sleep due to the influence of melatonin. A regular sleep cycle is vital to naturally increase the level of HGH in the body.

Evidence also indicates that sleep disturbances, particularly deprivation, are associated with an increased risk of obesity, diabetes, and insulin insensitivity, which may lower levels of HGH.

Among other tips, the Centers for Disease Control and Prevention (CDC) recommend exercising during the day to facilitate sleep at night. As both may help to naturally increase HGH, people can try to include regular exercise and adequate sleep in their routines to increase HGH levels.

HGH is a naturally occurring hormone released in the body by the pituitary gland. It has important functions in growth, metabolism, and muscle mass. Additional benefits may include improved learning, memory, bone health, and wound healing.

People may be able to naturally increase HGH levels through adequate sleep, exercise, and diet. However, a person should consult their doctor before making significant changes to their physical or dietary habits.

Additionally, illicit use of HGH is associated with risks. It is advisable that people only use prescription HGH to treat certain conditions, and not for other means.

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How can people increase HGH? - Medical News Today

Growth Hormones Fed to Beef Cattle Damage Human Health

Almost all beef cattle entering feedlots in the United States are given hormone implants to promote faster growth. The first product used for this purpose DES (diethylstilbestrol) was approved for use in beef cattle in 1954. An estimated two-thirds of the nation's beef cattle were treated with DES in 1956 (Marcus, 1994, cited in Swan et al., 2007).

Today, there are six anabolic steroids given, in various combinations, to nearly all animals entering conventional beef feedlots in the U.S. and Canada:

* Three natural steroids (estradiol, testosterone, and progesterone), and * Three synthetic hormones (the estrogen compound zeranol, the androgen trenbolone acetate, and progestin melengestrol acetate).

Anabolic steroids are typically used in combinations. Measurable levels of all the above growth-promoting hormones are found at slaughter in the muscle, fat, liver, kidneys and other organ meats. The Food and Drug Administration has set "acceptable daily intakes" (ADIs) for these animal drugs.

Questions and controversy over the impacts of these added hormones on human development and health have lingered for four decades. In 1988 the European Union banned the use of all hormone growth promoters. The ADIs on the books for years are based on traditional toxicity testing methods and do not reflect the capacity of these drugs, which are potent endocrine disruptors, to alter fetal and childhood development. According to Swan et al. (2007)

".the possible effects on human populations exposed to residues of anabolic sex hormones through meat consumption have never, to our knowledge, been studied. Theoretically, the fetus and the prepubertal child are particularly sensitive to exposure to sex steroids."

This gap in research is remarkable, given that every beef-eating American for over 50 years has been exposed to these hormones on a regular basis. To begin to explore possible impacts, Swan et al. (2007) carried out a study assessing the consequences of beef consumption by pregnant women on their adult male offspring. The families included in the study were recruited from the multicenter "Study for Future Families" (SFF).

The study team assessed sperm quantity and quality among 773 men. Data on beef consumption during pregnancy was available from the mothers of 387 men. These mothers consumed, on average, 4.3 beef meals per week, and were divided into a high beef consumption group (more than seven meals per week) and a low-consumption group (less than 7 per week).

The scientists compared sperm concentrations and quality among the men born to women in the high and low beef consumption groups. They found that:

* Sperm concentration (volume) was 24.3 percent higher in the sons of mothers in the "low" beef consumption group. * Almost 18 percent of the sons born to women in the high beef consumption group had sperm concentrations below the World Health Organization threshold for subfertility about three-times more than in the sons of women in the low consumption group.

The authors concluded that

"These findings suggest that maternal beef consumption is associated with lower sperm concentration and possible subfertility, associations that may be related to the presence of anabolic steroids and other xenobiotics in beef."

This study lends urgency to the long-recognized need for the FDA to reconsider the acceptable daily intakes of hormones used to promote growth in beef feedlots. This reassessment will, in all likelihood, be resisted by the animal drug and beef industries, and once begun, will take many years to be carried out. In the interim, families wanting to avoid the risk of developmental problems in their male children can do so by choosing organic beef.

Source: "Semen quality of fertile US males in relation to their mothers' beef consumption during pregnancy"

Authors: S.H. Swan, F. Liu, J.W. Overstreet, C. Brazil, and N.E. Skakkebaek

Journal: Human Reproduction, Advance Access published online March 28, 2007. Access the Full Text here.

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