Growth hormone

Last updated
Growth hormone 1 (pituitary)
Somatotropine.GIF
Growth hormone
Identifiers
Symbol GH1
NCBI gene 2688
HGNC 4261
OMIM 139250
RefSeq NM_022562
UniProt P01241
Other data
Locus Chr. 17 q22-q24
Search for
Structures Swiss-model
Domains InterPro
Growth hormone 2 (placental)
Identifiers
Symbol GH2
NCBI gene 2689
HGNC 4262
OMIM 139240
RefSeq NM_002059
UniProt P01242
Other data
Locus Chr. 17 q22-q24
Search for
Structures Swiss-model
Domains InterPro

Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in human development. GH also stimulates production of Insulin-like growth factor 1 (IGF-1) and increases the concentration of glucose and free fatty acids. [1] [2] It is a type of mitogen which is specific only to the receptors on certain types of cells. GH is a 191-amino acid, single-chain polypeptide that is synthesized, stored and secreted by somatotropic cells within the lateral wings of the anterior pituitary gland.

Contents

A recombinant form of HGH called somatropin (INN) is used as a prescription drug to treat children's growth disorders and adult growth hormone deficiency. In the United States, it is only available legally from pharmacies by prescription from a licensed health care provider. In recent years in the United States, some health care providers are prescribing growth hormone in the elderly to increase vitality. While legal, the efficacy and safety of this use for HGH has not been tested in a clinical trial. Many of the functions of HGH remain unknown. [3]

In its role as an anabolic agent, HGH has been used by competitors in sports since at least 1982, and has been banned by the IOC and NCAA. Traditional urine analysis does not detect doping with HGH, so the ban was not enforced until the early 2000s, when blood tests that could distinguish between natural and artificial HGH were starting to be developed. Blood tests conducted by WADA at the 2004 Olympic Games in Athens, Greece, targeted primarily HGH. [3] Use of the drug for performance enhancement is not currently approved by the FDA.

GH has been studied for use in raising livestock more efficiently in industrial agriculture and several efforts have been made to obtain governmental approval to use GH in livestock production. These uses have been controversial. In the United States, the only FDA-approved use of GH for livestock is the use of a cow-specific form of GH called bovine somatotropin for increasing milk production in dairy cows. Retailers are permitted to label containers of milk as produced with or without bovine somatotropin.

Nomenclature

The names somatotropin (STH) or somatotropic hormone refer to the growth hormone produced naturally in animals and extracted from carcasses. Hormone extracted from human cadavers is abbreviated hGH. The main growth hormone produced by recombinant DNA technology has the approved generic name (INN) somatropin and the brand name Humatrope, [4] and is properly abbreviated rhGH in the scientific literature. Since its introduction in 1992 Humatrope has been a banned sports doping agent, [5] and in this context is referred to as HGH.

The term growth hormone has been incorrectly applied to refer to anabolic sex hormones in the European beef hormone controversy, which initially restricts the use of estradiol, progesterone, testosterone, zeranol, melengestrol acetate and trenbolone acetate. [6]

Biology

Gene

Genes for human growth hormone, known as growth hormone 1 (somatotropin; pituitary growth hormone) and growth hormone 2 (placental growth hormone; growth hormone variant), are localized in the q22-24 region of chromosome 17 [7] [8] and are closely related to human chorionic somatomammotropin (also known as placental lactogen) genes. GH, human chorionic somatomammotropin, and prolactin belong to a group of homologous hormones with growth-promoting and lactogenic activity.

Structure

The major isoform of the human growth hormone is a protein of 191 amino acids and a molecular weight of 22,124 daltons. The structure includes four helices necessary for functional interaction with the GH receptor. It appears that, in structure, GH is evolutionarily homologous to prolactin and chorionic somatomammotropin. Despite marked structural similarities between growth hormone from different species, only human and Old World monkey growth hormones have significant effects on the human growth hormone receptor. [9]

Several molecular isoforms of GH exist in the pituitary gland and are released to blood. In particular, a variant of approximately 20 kDa originated by an alternative splicing is present in a rather constant 1:9 ratio, [10] while recently an additional variant of ~ 23-24 kDa has also been reported in post-exercise states at higher proportions. [11] This variant has not been identified, but it has been suggested to coincide with a 22 kDa glycosylated variant of 23 kDa identified in the pituitary gland. [12] Furthermore, these variants circulate partially bound to a protein (growth hormone-binding protein, GHBP), which is the truncated part of the growth hormone receptor, and an acid-labile subunit (ALS).

Regulation

Flowchart showing hormonal regulation of growth 1809 Hormonal Regulation of Growth.jpg
Flowchart showing hormonal regulation of growth

Secretion of growth hormone (GH) in the pituitary is regulated by the neurosecretory nuclei of the hypothalamus. These cells release the peptides growth hormone-releasing hormone (GHRH or somatocrinin) and growth hormone-inhibiting hormone (GHIH or somatostatin) into the hypophyseal portal venous blood surrounding the pituitary. GH release in the pituitary is primarily determined by the balance of these two peptides, which in turn is affected by many physiological stimulators (e.g., exercise, nutrition, sleep) and inhibitors (e.g., free fatty acids) of GH secretion. [13]

Somatotropic cells in the anterior pituitary gland then synthesize and secrete GH in a pulsatile manner, in response to these stimuli by the hypothalamus. The largest and most predictable of these GH peaks occurs about an hour after onset of sleep with plasma levels of 13 to 72 ng/mL. [14] Maximal secretion of GH may occur within minutes of the onset of slow-wave (SW) sleep (stage III or IV). [15] Otherwise there is wide variation between days and individuals. Nearly fifty percent of GH secretion occurs during the third and fourth NREM sleep stages. [16] Surges of secretion during the day occur at 3- to 5-hour intervals. [3] The plasma concentration of GH during these peaks may range from 5 to even 45 ng/mL. [17] Between the peaks, basal GH levels are low, usually less than 5 ng/mL for most of the day and night. [14] Additional analysis of the pulsatile profile of GH described in all cases less than 1 ng/ml for basal levels while maximum peaks were situated around 10-20 ng/mL. [18] [19]

A number of factors are known to affect GH secretion, such as age, sex, diet, exercise, stress, and other hormones. [3] Young adolescents secrete GH at the rate of about 700 μg/day, while healthy adults secrete GH at the rate of about 400 μg/day. [20] Sleep deprivation generally suppresses GH release, particularly after early adulthood. [21]

Stimulators[ quantify ] of growth hormone (GH) secretion include:

Inhibitors[ quantify ] of GH secretion include:

In addition to control by endogenous and stimulus processes, a number of foreign compounds (xenobiotics such as drugs and endocrine disruptors) are known to influence GH secretion and function. [38]

Function

Main pathways in endocrine regulation of growth Endocrine growth regulation.svg
Main pathways in endocrine regulation of growth

Effects of growth hormone on the tissues of the body can generally be described as anabolic (building up). Like most other peptide hormones, GH acts by interacting with a specific receptor on the surface of cells.

Increased height during childhood is the most widely known effect of GH. Height appears to be stimulated by at least two mechanisms:

  1. Because polypeptide hormones are not fat-soluble, they cannot penetrate cell membranes. Thus, GH exerts some of its effects by binding to receptors on target cells, where it activates the MAPK/ERK pathway. [39] Through this mechanism GH directly stimulates division and multiplication of chondrocytes of cartilage.
  2. GH also stimulates, through the JAK-STAT signaling pathway, [39] the production of insulin-like growth factor 1 (IGF-1, formerly known as somatomedin C), a hormone homologous to proinsulin. [40] The liver is a major target organ of GH for this process and is the principal site of IGF-1 production. IGF-1 has growth-stimulating effects on a wide variety of tissues. Additional IGF-1 is generated within target tissues, making it what appears to be both an endocrine and an autocrine/paracrine hormone. IGF-1 also has stimulatory effects on osteoblast and chondrocyte activity to promote bone growth.

In addition to increasing height in children and adolescents, growth hormone has many other effects on the body:

Biochemistry

GH has a short biological half-life of about 10 to 20 minutes. [45] [46]

Clinical significance

Excess

The most common disease of GH excess is a pituitary tumor composed of somatotroph cells of the anterior pituitary. These somatotroph adenomas are benign and grow slowly, gradually producing more and more GH. For years, the principal clinical problems are those of GH excess. Eventually, the adenoma may become large enough to cause headaches, impair vision by pressure on the optic nerves, or cause deficiency of other pituitary hormones by displacement.

Prolonged GH excess thickens the bones of the jaw, fingers and toes, resulting in heaviness of the jaw and increased size of digits, referred to as acromegaly. Accompanying problems can include sweating, pressure on nerves (e.g. carpal tunnel syndrome), muscle weakness, excess sex hormone-binding globulin (SHBG), insulin resistance or even a rare form of type 2 diabetes, and reduced sexual function.

GH-secreting tumors are typically recognized in the fifth decade of life. It is extremely rare for such a tumor to occur in childhood, but, when it does, the excessive GH can cause excessive growth, traditionally referred to as pituitary gigantism.

Surgical removal is the usual treatment for GH-producing tumors. In some circumstances, focused radiation or a GH antagonist such as pegvisomant may be employed to shrink the tumor or block function. Other drugs like octreotide (somatostatin agonist) and bromocriptine (dopamine agonist) can be used to block GH secretion because both somatostatin and dopamine negatively inhibit GHRH-mediated GH release from the anterior pituitary. [47]

Deficiency

The effects of growth hormone (GH) deficiency vary depending on the age at which they occur. Alterations in somatomedin can result in growth hormone deficiency with two known mechanisms; failure of tissues to respond to somatomedin, or failure of the liver to produce somatomedin. [48] Major manifestations of GH deficiency in children are growth failure, the development of a short stature, and delayed sexual maturity. In adults, somatomedin alteration contributes to increased osteoclast activity, resulting in weaker bones that are more prone to pathologic fracture and osteoporosis. [48] However, deficiency is rare in adults, with the most common cause being a pituitary adenoma. [49] Other adult causes include a continuation of a childhood problem, other structural lesions or trauma, and very rarely idiopathic GHD. [49]

Adults with GHD "tend to have a relative increase in fat mass and a relative decrease in muscle mass and, in many instances, decreased energy and quality of life". [49]

Diagnosis of GH deficiency involves a multiple-step diagnostic process, usually culminating in GH stimulation tests to see if the patient's pituitary gland will release a pulse of GH when provoked by various stimuli.

Psychological effects

Quality of life

Several studies, primarily involving patients with GH deficiency, have suggested a crucial role of GH in both mental and emotional well-being and maintaining a high energy level. Adults with GH deficiency often have higher rates of depression than those without. [50] While GH replacement therapy has been proposed to treat depression as a result of GH deficiency, the long-term effects of such therapy are unknown. [50]

Cognitive function

GH has also been studied in the context of cognitive function, including learning and memory. [51] GH in humans appears to improve cognitive function and may be useful in the treatment of patients with cognitive impairment that is a result of GH deficiency. [51]

Medical uses

Replacement therapy

GH is used as replacement therapy in adults with GH deficiency of either childhood-onset or adult-onset (usually as a result of an acquired pituitary tumor). In these patients, benefits have variably included reduced fat mass, increased lean mass, increased bone density, improved lipid profile, reduced cardiovascular risk factors, and improved psychosocial well-being. Long acting growth hormone (LAGH) analogues are now available for treating growth hormone deficiency both in children and adults. These are once weekly injections as compared to conventional growth hormone which has to be taken as daily injections. LAGH injection 4 times a month has been found to be as safe and effective as daily growth hormone injections. [52]

Other approved uses

GH can be used to treat conditions that produce short stature but are not related to deficiencies in GH. However, results are not as dramatic when compared to short stature that is solely attributable to deficiency of GH. Examples of other causes of shortness often treated with GH are Turner syndrome, Growth failure secondary to chronic kidney disease in children, [53] Prader–Willi syndrome, intrauterine growth restriction, and severe idiopathic short stature. Higher ("pharmacologic") doses are required to produce significant acceleration of growth in these conditions, producing blood levels well above normal ("physiologic").[ citation needed ]

One version of rHGH has also been FDA approved for maintaining muscle mass in wasting due to AIDS. [54]

Off-label use

Off-label prescription of HGH is controversial and may be illegal. [55]

Claims for GH as an anti-aging treatment date back to 1990 when the New England Journal of Medicine published a study wherein GH was used to treat 12 men over 60. [56] At the conclusion of the study, all the men showed statistically significant increases in lean body mass and bone mineral density, while the control group did not. The authors of the study noted that these improvements were the opposite of the changes that would normally occur over a 10- to 20-year aging period. Despite the fact the authors at no time claimed that GH had reversed the aging process itself, their results were misinterpreted as indicating that GH is an effective anti-aging agent. [57] [58] [59] This has led to organizations such as the controversial American Academy of Anti-Aging Medicine promoting the use of this hormone as an "anti-aging agent". [60]

A Stanford University School of Medicine meta-analysis of clinical studies on the subject published in early 2007 showed that the application of GH on healthy elderly patients increased muscle by about 2 kg and decreased body fat by the same amount. [57] However, these were the only positive effects from taking GH. No other critical factors were affected, such as bone density, cholesterol levels, lipid measurements, maximal oxygen consumption, or any other factor that would indicate increased fitness. [57] Researchers also did not discover any gain in muscle strength, which led them to believe that GH merely let the body store more water in the muscles rather than increase muscle growth. This would explain the increase in lean body mass.

GH has also been used experimentally to treat multiple sclerosis, to enhance weight loss in obesity, as well as in fibromyalgia, heart failure, Crohn's disease and ulcerative colitis, and burns. GH has also been used experimentally in patients with short bowel syndrome to lessen the requirement for intravenous total parenteral nutrition.

In 1990, the US Congress passed an omnibus crime bill, the Crime Control Act of 1990, that amended the Federal Food, Drug, and Cosmetic Act, that classified anabolic steroids as controlled substances and added a new section that stated that a person who "knowingly distributes, or possesses with intent to distribute, human growth hormone for any use in humans other than the treatment of a disease or other recognized medical condition, where such use has been authorized by the Secretary of Health and Human Services" has committed a felony. [61] [62]

The Drug Enforcement Administration of the US Department of Justice considers off-label prescribing of HGH to be illegal, and to be a key path for illicit distribution of HGH. [55] This section has also been interpreted by some doctors, most notably [63] the authors of a commentary article published in the Journal of the American Medical Association in 2005, as meaning that prescribing HGH off-label may be considered illegal. [64] And some articles in the popular press, such as those criticizing the pharmaceutical industry for marketing drugs for off-label use (with concern of ethics violations) have made strong statements about whether doctors can prescribe HGH off-label: "Unlike other prescription drugs, HGH may be prescribed only for specific uses. U.S. sales are limited by law to treat a rare growth defect in children and a handful of uncommon conditions like short bowel syndrome or Prader-Willi syndrome, a congenital disease that causes reduced muscle tone and a lack of hormones in sex glands." [65] [66] At the same time, anti-aging clinics where doctors prescribe, administer, and sell HGH to people are big business. [65] [67] In a 2012 article in Vanity Fair , when asked how HGH prescriptions far exceed the number of adult patients estimated to have HGH-deficiency, Dragos Roman, who leads a team at the FDA that reviews drugs in endocrinology, said "The F.D.A. doesn't regulate off-label uses of H.G.H. Sometimes it's used appropriately. Sometimes it's not." [67]

Side effects

Injection site reactions are common. More rarely, patients can experience joint swelling, joint pain, carpal tunnel syndrome, and an increased risk of diabetes. [57] In some cases, the patient can produce an immune response against GH. GH may also be a risk factor for Hodgkin's lymphoma. [68]

One survey of adults that had been treated with replacement cadaver GH (which has not been used anywhere in the world since 1985) during childhood showed a mildly increased incidence of colon cancer and prostate cancer, but linkage with the GH treatment was not established. [69]

Performance enhancement

The first description of the use of GH as a doping agent was Dan Duchaine's "Underground Steroid handbook" which emerged from California in 1982; it is not known where and when GH was first used this way. [70]

Athletes in many sports have used human growth hormone in order to attempt to enhance their athletic performance. Some recent studies have not been able to support claims that human growth hormone can improve the athletic performance of professional male athletes. [71] [72] [73] Many athletic societies ban the use of GH and will issue sanctions against athletes who are caught using it. However, because GH is a potent endogenous protein, it is very difficult to detect GH doping. In the United States, GH is legally available only by prescription from a medical doctor.

Dietary supplements

To capitalize on the idea that GH might be useful to combat aging, companies selling dietary supplements have websites selling products linked to GH in the advertising text, with medical-sounding names described as "HGH Releasers". Typical ingredients include amino acids, minerals, vitamins, and/or herbal extracts, the combination of which are described as causing the body to make more GH with corresponding beneficial effects. In the United States, because these products are marketed as dietary supplements, it is illegal for them to contain GH, which is a drug. Also, under United States law, products sold as dietary supplements cannot have claims that the supplement treats or prevents any disease or condition, and the advertising material must contain a statement that the health claims are not approved by the FDA. The FTC and the FDA do enforce the law when they become aware of violations. [74]

Agricultural use

In the United States, it is legal to give a bovine GH to dairy cows to increase milk production, and is legal to use GH in raising cows for beef; see article on Bovine somatotropin, cattle feeding, dairy farming and the beef hormone controversy.

The use of GH in poultry farming is illegal in the United States. [75] [76] Similarly, no chicken meat for sale in Australia is administered hormones. [77]

Several companies have attempted to have a version of GH for use in pigs (porcine somatotropin) approved by the FDA but all applications have been withdrawn. [78]

Drug development history

Genentech pioneered the use of recombinant human growth hormone for human therapy, which was approved by the FDA in 1985.

Prior to its production by recombinant DNA technology, growth hormone used to treat deficiencies was extracted from the pituitary glands of cadavers. Attempts to create a wholly synthetic HGH failed. Limited supplies of HGH resulted in the restriction of HGH therapy to the treatment of idiopathic short stature. [79] Very limited clinical studies of growth hormone derived from an Old World monkey, the rhesus macaque, were conducted by John C. Beck and colleagues in Montreal, in the late 1950s. [80] The study published in 1957, which was conducted on "a 13-year-old male with well-documented hypopituitarism secondary to a crainiophyaryngioma," found that: "Human and monkey growth hormone resulted in a significant enhancement of nitrogen storage ... (and) there was a retention of potassium, phosphorus, calcium, and sodium. ... There was a gain in body weight during both periods. ... There was a significant increase in urinary excretion of aldosterone during both periods of administration of growth hormone. This was most marked with the human growth hormone. ... Impairment of the glucose tolerance curve was evident after 10 days of administration of the human growth hormone. No change in glucose tolerance was demonstrable on the fifth day of administration of monkey growth hormone." [80] The other study, published in 1958, was conducted on six people: the same subject as the Science paper; an 18-year-old male with statural and sexual retardation and a skeletal age of between 13 and 14 years; a 15-year-old female with well-documented hypopituitarism secondary to a craniopharyngioma; a 53-year-old female with carcinoma of the breast and widespread skeletal metastases; a 68-year-old female with advanced postmenopausal osteoporosis; and a healthy 24-year-old medical student without any clinical or laboratory evidence of systemic disease. [81]

In 1985, unusual cases of Creutzfeldt–Jakob disease were found in individuals that had received cadaver-derived HGH ten to fifteen years previously. Based on the assumption that infectious prions causing the disease were transferred along with the cadaver-derived HGH, cadaver-derived HGH was removed from the market. [20]

In 1985, biosynthetic human growth hormone replaced pituitary-derived human growth hormone for therapeutic use in the U.S. and elsewhere.

As of 2005, recombinant growth hormones available in the United States (and their manufacturers) included Nutropin (Genentech), Humatrope (Lilly), Genotropin (Pfizer), Norditropin (Novo), and Saizen (Merck Serono). In 2006, the U.S. Food and Drug Administration (FDA) approved a version of rHGH called Omnitrope (Sandoz). [82] A sustained-release form of growth hormone, Nutropin Depot (Genentech and Alkermes) was approved by the FDA in 1999, allowing for fewer injections (every 2 or 4 weeks instead of daily); however, the product was discontinued by Genentech/Alkermes in 2004 for financial reasons (Nutropin Depot required significantly more resources to produce than the rest of the Nutropin line [83] ).

See also

Related Research Articles

<span class="mw-page-title-main">Gigantism</span> Human growth disorder

Gigantism, also known as giantism, is a condition characterized by excessive growth and height significantly above average. In humans, this condition is caused by over-production of growth hormone in childhood.

<span class="mw-page-title-main">Growth hormone deficiency</span> Medical condition

Growth hormone deficiency (GHD), or human growth hormone deficiency, is a medical condition resulting from not enough growth hormone (GH). Generally the most noticeable symptom is that an individual attains a short height. Newborns may also present low blood sugar or a small penis size. In adults there may be decreased muscle mass, high cholesterol levels, or poor bone density.

Growth hormone therapy refers to the use of growth hormone (GH) as a prescription medication—it is one form of hormone therapy. Growth hormone is a peptide hormone secreted by the pituitary gland that stimulates growth and cell reproduction. In the past, growth hormone was extracted from human pituitary glands. Growth hormone is now produced by recombinant DNA technology and is prescribed for a variety of reasons. GH therapy has been a focus of social and ethical controversies for 50 years.

<span class="mw-page-title-main">Insulin-like growth factor 1</span> Protein-coding gene in the species Homo sapiens

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.

Controversies regarding the use of human growth hormone (HGH) as treatment method have centered on the claims, products, and businesses related to the use of growth hormone as an anti-aging therapy. Most of these controversies fall into two categories:

  1. Claims of exaggerated, misleading, or unfounded assertions that growth hormone treatment safely and effectively slows or reverses the effects of aging.
  2. The sale of products that fraudulently or misleadingly purport to be growth hormone or to increase the user's own secretion of natural human growth hormone to a beneficial degree.
<span class="mw-page-title-main">Endocrine gland</span> Glands of the endocrine system that secrete hormones to blood

Endocrine glands are ductless glands of the endocrine system that secrete their products, hormones, directly into the blood. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testicles, thyroid gland, parathyroid gland, hypothalamus and adrenal glands. The hypothalamus and pituitary glands are neuroendocrine organs.

<span class="mw-page-title-main">Octreotide</span> Octapeptide that mimics natural somatostatin pharmacologically

Octreotide, sold under the brand name Sandostatin among others, is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone. It was first synthesized in 1979 by the chemist Wilfried Bauer, and binds predominantly to the somatostatin receptors SSTR2 and SSTR5.

Growth hormone–releasing hormone (GHRH), also known as somatocrinin or by several other names in its endogenous forms and as somatorelin (INN) in its pharmaceutical form, is a releasing hormone of growth hormone (GH). It is a 44-amino acid peptide hormone produced in the arcuate nucleus of the hypothalamus.

<span class="mw-page-title-main">Somatomedin</span> Group of proteins responsible for both promotion and inhibition of cellular growth

Somatomedins are a group of proteins produced predominantly by the liver when growth hormones act on target tissue. Somatomedins inhibit the release of growth hormones by acting directly on anterior pituitary and by stimulating the secretion of somatostatin from the hypothalamus.

<span class="mw-page-title-main">Laron syndrome</span> Medical condition

Laron syndrome (LS), also known as growth hormone insensitivity or growth hormone receptor deficiency (GHRD), is an autosomal recessive disorder characterized by a lack of insulin-like growth factor 1 production in response to growth hormone. It is usually caused by inherited growth hormone receptor (GHR) mutations.

Pegvisomant, sold under the brand name Somavert, is a growth hormone receptor antagonist used in the treatment of acromegaly. It is primarily used if the pituitary gland tumor causing the acromegaly cannot be controlled with surgery or radiation, and the use of somatostatin analogues is unsuccessful, but is also effective as a monotherapy. It is delivered as a powder that is mixed with water and injected under the skin.

CJC-1295, also known as DAC:GRF, is a synthetic analogue of growth hormone-releasing hormone (GHRH) and a growth hormone secretagogue (GHS) which was developed by ConjuChem Biotechnologies. It is a modified form of GHRH (1-29) with improved pharmacokinetics, especially in regard to half-life.

<span class="mw-page-title-main">Ibutamoren</span> Experimental drug

Ibutamoren is a potent, long-acting, orally-active, selective, and non-peptide agonist of the ghrelin receptor and a growth hormone secretagogue, mimicking the growth hormone (GH)-stimulating action of the endogenous hormone ghrelin. It has been shown to increase the secretion of several hormones including GH and insulin-like growth factor 1 (IGF-1) and produces sustained increases in the plasma levels of these hormones without affecting cortisol levels.

<span class="mw-page-title-main">Tabimorelin</span> Chemical compound

Tabimorelin (INN) is a drug which acts as a potent, orally-active agonist of the ghrelin/growth hormone secretagogue receptor (GHSR) and growth hormone secretagogue, mimicking the effects of the endogenous peptide agonist ghrelin as a stimulator of growth hormone (GH) release. It was one of the first GH secretagogues developed and is largely a modified polypeptide, but it is nevertheless orally-active in vivo. Tabimorelin produced sustained increases in levels of GH and insulin-like growth factor 1 (IGF-1), along with smaller transient increases in levels of other hormones such as adrenocorticotropic hormone (ACTH), cortisol, and prolactin. However actual clinical effects in adults with growth hormone deficiency were limited, with only the most severely GH-deficient patients showing significant benefit, and tabimorelin was also found to act as a CYP3A4 inhibitor which could cause it to have undesirable interactions with other drugs.

<span class="mw-page-title-main">Acromegaly</span> Human disease that results in excess growth of certain parts of the body

Acromegaly is a disorder that results in excess growth of certain parts of the human body. It is caused by excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There may also be an enlargement of the forehead, jaw, and nose. Other symptoms may include joint pain, thicker skin, deepening of the voice, headaches, and problems with vision. Complications of the disease may include type 2 diabetes, sleep apnea, and high blood pressure.

Growth hormones in sports refers to the use of growth hormones for athletic enhancement, as opposed to growth hormone treatment for medical therapy. Human Growth Hormone is a prescription medication in the US, meaning that its distribution and use without a prescription is illegal. There is limited evidence that GH doping improves athletic performance, although the perception that it does is common in the sporting community. Potential side effects of long term GH doping could mirror the symptoms found in sufferers of acromegaly, a disease in which the anterior pituitary gland produces excess growth hormone. These symptoms include swelling of the hands and feet, joint pain, fluid retention, and excessive sweating.

Cyril Y. Bowers, M.D., emeritus professor of medicine at Tulane University School of Medicine, attended medical school at the University of Oregon and did an internship at the University of Washington. He then studied biochemistry at Cornell University and attended the postgraduate school of medicine at the University of Pennsylvania. From 1961-2004 he was the director of the Section of Endocrinology & Metabolism in the department of medicine at Tulane University School of Medicine. Bowers has served on the editorial board of several endocrine journals, was a member of the National Institute of Diabetes and Digestive and Kidney Diseases Study Section for eight years and has written over 400 articles in peer-reviewed journals, including chapters in books and over 200 abstracts.

Growth hormone secretagogues or GH secretagogues (GHSs) are a class of drugs which act as secretagogues of growth hormone (GH). They include agonists of the ghrelin/growth hormone secretagogue receptor (GHSR), such as ghrelin (lenomorelin), pralmorelin (GHRP-2), GHRP-6, examorelin (hexarelin), ipamorelin, and ibutamoren (MK-677), and agonists of the growth hormone-releasing hormone receptor (GHRHR), such as growth hormone-releasing hormone, CJC-1295, sermorelin, and tesamorelin.

<span class="mw-page-title-main">Tesamorelin</span> Pharmaceutical drug

Tesamorelin (INN) is a synthetic form of growth-hormone-releasing hormone (GHRH) which is used in the treatment of HIV-associated lipodystrophy, approved initially in 2010. It is produced and developed by Theratechnologies, Inc. of Canada. The drug is a synthetic peptide consisting of all 44 amino acids of human GHRH with the addition of a trans-3-hexenoic acid group.

<span class="mw-page-title-main">Hypothalamic–pituitary–somatotropic axis</span>

The hypothalamic–pituitary–somatotropic axis, or hypothalamic–pituitary–somatic axis, also known as the hypothalamic–pituitary–growth axis, is a hypothalamic–pituitary axis which includes the secretion of growth hormone from the somatotropes of the pituitary gland into the circulation and the subsequent stimulation of insulin-like growth factor 1 production by GH in tissues such as, namely, the liver. Other hypothalamic–pituitary hormones such as growth hormone-releasing hormone, growth hormone-inhibiting hormone, and ghrelin (GHS) are involved in the control of GH secretion from the pituitary gland. The HPS axis is involved in postnatal human growth. Individuals with growth hormone deficiency or Laron syndrome show symptoms like short stature, dwarfism and obesity, but are also protected from some forms of cancer. Conversely, acromegaly and gigantism are conditions of GH and IGF-1 excess usually due to a pituitary tumor, and are characterized by overgrowth and tall stature.

References

  1. ↑ Ranabir S, Reetu K (January 2011). "Stress and hormones". Indian Journal of Endocrinology and Metabolism. 15 (1): 18–22. doi: 10.4103/2230-8210.77573 . PMC   3079864 . PMID   21584161.
  2. ↑ Greenwood FC, Landon J (April 1966). "Growth hormone secretion in response to stress in man". Nature. 210 (5035): 540–1. Bibcode:1966Natur.210..540G. doi:10.1038/210540a0. PMID   5960526. S2CID   1829264.
  3. 1 2 3 4 5 Powers M (2005). "Performance-Enhancing Drugs". In Leaver-Dunn D, Houglum J, Harrelson GL (eds.). Principles of Pharmacology for Athletic Trainers. Slack Incorporated. pp. 331–332. ISBN   978-1-55642-594-3.
  4. ↑ Daniels ME (1992). "Lilly's Humatrope Experience". Nature Biotechnology. 10 (7): 812. doi: 10.1038/nbt0792-812a . S2CID   46453790.
  5. ↑ Saugy M, Robinson N, Saudan C, Baume N, Avois L, Mangin P (July 2006). "Human growth hormone doping in sport". British Journal of Sports Medicine. 40 (Suppl 1): i35–9. doi:10.1136/bjsm.2006.027573. PMC   2657499 . PMID   16799101.
  6. ↑ William A Kerr & Jill E Hobbs (February 2002). "The North American-European Union Dispute Over Beef Produced Using Growth Hormones: A Major Test for the New International Trade Regime". The World Economy. 25 (2): 283–296. doi:10.1111/1467-9701.00431. S2CID   154707486.
  7. ↑ "GH1 growth hormone 1 (Homo sapiens) - Gene". National Center for Biotechnology Information, U.S. National Library of Medicine.
  8. ↑ "GH2 growth hormone 2 (Homo sapiens) - Gene". National Center for Biotechnology Information, U.S. National Library of Medicine.
  9. ↑ Yi S, Bernat B, Pál G, Kossiakoff A, Li WH (July 2002). "Functional promiscuity of squirrel monkey growth hormone receptor toward both primate and nonprimate growth hormones". Molecular Biology and Evolution. 19 (7): 1083–92. doi: 10.1093/oxfordjournals.molbev.a004166 . PMID   12082127.
  10. ↑ Leung KC, Howe C, Gui LY, Trout G, Veldhuis JD, Ho KK (October 2002). "Physiological and pharmacological regulation of 20-kDa growth hormone". American Journal of Physiology. Endocrinology and Metabolism. 283 (4): E836–43. doi:10.1152/ajpendo.00122.2002. PMID   12217902.
  11. ↑ Kohler M, Püschel K, Sakharov D, Tonevitskiy A, Schänzer W, Thevis M (November 2008). "Detection of recombinant growth hormone in human plasma by a 2-D PAGE method". Electrophoresis. 29 (22): 4495–502. doi:10.1002/elps.200800221. PMID   19003817. S2CID   22525768.
  12. ↑ Bustamante JJ, Gonzalez L, Carroll CA, Weintraub ST, Aguilar RM, Muñoz J, Martinez AO, Haro LS (July 2009). "O-Glycosylated 24 kDa human growth hormone has a mucin-like biantennary disialylated tetrasaccharide attached at Thr-60". Proteomics. 9 (13): 3474–88. doi:10.1002/pmic.200800989. PMC   2904392 . PMID   19579232.
  13. ↑ Bartholomew EF, Martini F, Nath JL (2009). Fundamentals of anatomy & physiology. Upper Saddle River, NJ: Pearson Education Inc. pp. 616–617. ISBN   978-0-321-53910-6.
  14. 1 2 Takahashi Y, Kipnis DM, Daughaday WH (September 1968). "Growth hormone secretion during sleep". The Journal of Clinical Investigation. 47 (9): 2079–90. doi:10.1172/JCI105893. PMC   297368 . PMID   5675428.
  15. ↑ Van Cauter E, Copinschi G (April 2000). "Interrelationships between growth hormone and sleep". Growth Hormone & IGF Research. 10 (Suppl B): S57–62. doi:10.1016/s1096-6374(00)80011-8. PMID   10984255.
  16. ↑ Mehta A, Hindmarsh PC (2002). "The use of somatropin (recombinant growth hormone) in children of short stature". Paediatric Drugs. 4 (1): 37–47. doi:10.2165/00128072-200204010-00005. PMID   11817985. S2CID   23663131.
  17. ↑ Natelson BH, Holaday J, Meyerhoff J, Stokes PE (August 1975). "Temporal changes in growth hormone, cortisol, and glucose: relation to light onset and behavior". The American Journal of Physiology. 229 (2): 409–15. doi: 10.1152/ajplegacy.1975.229.2.409 . PMID   808970.
  18. ↑ Nindl BC, Hymer WC, Deaver DR, Kraemer WJ (July 2001). "Growth hormone pulsatility profile characteristics following acute heavy resistance exercise". Journal of Applied Physiology. 91 (1): 163–72. doi:10.1152/jappl.2001.91.1.163. PMID   11408427. S2CID   16101442.
  19. ↑ Juul A, Jørgensen JO, Christiansen JS, Müller J, Skakkeboek NE (1995). "Metabolic effects of GH: a rationale for continued GH treatment of GH-deficient adults after cessation of linear growth". Hormone Research. 44 Suppl 3 (3): 64–72. doi:10.1159/000184676. PMID   8719443.
  20. 1 2 Gardner DG, Shoback D (2007). Greenspan's Basic and Clinical Endocrinology (8th ed.). New York: McGraw-Hill Medical. pp. 193–201. ISBN   978-0-07-144011-0.
  21. ↑ Mullington J, Hermann D, Holsboer F, Pollmächer T (September 1996). "Age-dependent suppression of nocturnal growth hormone levels during sleep deprivation". Neuroendocrinology. 64 (3): 233–41. doi:10.1159/000127122. PMID   8875441. S2CID   3328167.
  22. ↑ Lin-Su K, Wajnrajch MP (December 2002). "Growth Hormone Releasing Hormone (GHRH) and the GHRH Receptor". Reviews in Endocrine & Metabolic Disorders. 3 (4): 313–23. doi:10.1023/A:1020949507265. PMID   12424433. S2CID   6263928.
  23. ↑ Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DG, Ghatei MA, Bloom SR (November 2000). "The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion". Endocrinology. 141 (11): 4325–8. doi: 10.1210/endo.141.11.7873 . PMID   11089570.
  24. ↑ Meinhardt UJ, Ho KK (October 2006). "Modulation of growth hormone action by sex steroids". Clinical Endocrinology. 65 (4): 413–22. doi: 10.1111/j.1365-2265.2006.02676.x . PMID   16984231. S2CID   20688016.
  25. 1 2 3 Low LC (1991). "Growth hormone-releasing hormone: clinical studies and therapeutic aspects". Neuroendocrinology. 53 (Suppl 1): 37–40. doi:10.1159/000125793. PMID   1901390.
  26. ↑ Fedi M, Bach LA, Berkovic SF, Willoughby JO, Scheffer IE, Reutens DC (February 2008). "Association of a nicotinic receptor mutation with reduced height and blunted physostigmine-stimulated growth hormone release". The Journal of Clinical Endocrinology and Metabolism. 93 (2): 634–7. doi: 10.1210/jc.2007-1611 . PMID   18042647.
  27. ↑ Wilkins JN, Carlson HE, Van Vunakis H, Hill MA, Gritz E, Jarvik ME (1982). "Nicotine from cigarette smoking increases circulating levels of cortisol, growth hormone, and prolactin in male chronic smokers". Psychopharmacology. 78 (4): 305–8. doi:10.1007/BF00433730. PMID   6818588. S2CID   37559511.
  28. ↑ Coiro V, d'Amato L, Borciani E, Rossi G, Camellini L, Maffei ML, Pignatti D, Chiodera P (November 1984). "Nicotine from cigarette smoking enhances clonidine-induced increase of serum growth hormone concentrations in men". British Journal of Clinical Pharmacology. 18 (5): 802–5. doi:10.1111/j.1365-2125.1984.tb02547.x. PMC   1463553 . PMID   6508989.
  29. ↑ Alba-Roth J, Müller OA, Schopohl J, von Werder K (December 1988). "Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion". The Journal of Clinical Endocrinology and Metabolism. 67 (6): 1186–9. doi:10.1210/jcem-67-6-1186. PMID   2903866. S2CID   7488757.
  30. ↑ Samuels, Ebony R; Hou, Ruihua H; Langley, Robert W; Szabadi, Elemer; Bradshaw, Christopher M (June 19, 2007). "Comparison of pramipexole with and without domperidone co-administration on alertness, autonomic, and endocrine functions in healthy volunteers". British Journal of Clinical Pharmacology. 64 (5): 591–602. doi:10.1111/j.1365-2125.2007.02938.x. ISSN   0306-5251. PMC   2203276 . PMID   17578485.
  31. ↑ Van Cauter E, Latta F, Nedeltcheva A, Spiegel K, Leproult R, Vandenbril C, Weiss R, Mockel J, Legros JJ, Copinschi G (June 2004). "Reciprocal interactions between the GH axis and sleep". Growth Hormone & IGF Research. 14 Suppl A: S10–7. doi:10.1016/j.ghir.2004.03.006. PMID   15135771.
  32. ↑ Quabbe HJ, Luyckx AS, L'age M, Schwarz C (August 1983). "Growth hormone, cortisol, and glucagon concentrations during plasma free fatty acid depression: different effects of nicotinic acid and an adenosine derivative (BM 11.189)". The Journal of Clinical Endocrinology and Metabolism. 57 (2): 410–4. doi:10.1210/jcem-57-2-410. PMID   6345570.
  33. ↑ Nørrelund H (April 2005). "The metabolic role of growth hormone in humans with particular reference to fasting". Growth Hormone & IGF Research. 15 (2): 95–122. doi:10.1016/j.ghir.2005.02.005. PMID   15809014.
  34. ↑ "Greenspan's Basic & Clinical Endocrinology 10th Edition"
  35. ↑ Kanaley JA, Weltman JY, Veldhuis JD, Rogol AD, Hartman ML, Weltman A (November 1997). "Human growth hormone response to repeated bouts of aerobic exercise". Journal of Applied Physiology. 83 (5): 1756–61. doi:10.1152/jappl.1997.83.5.1756. PMID   9375348.
  36. ↑ Guillemin R, Gerich JE (1976). "Somatostatin: physiological and clinical significance". Annual Review of Medicine. 27: 379–88. doi:10.1146/annurev.me.27.020176.002115. PMID   779605.
  37. ↑ Allen DB (September 1996). "Growth suppression by glucocorticoid therapy". Endocrinology and Metabolism Clinics of North America. 25 (3): 699–717. doi:10.1016/S0889-8529(05)70348-0. PMID   8879994.
  38. ↑ Scarth JP (2006). "Modulation of the growth hormone-insulin-like growth factor (GH-IGF) axis by pharmaceutical, nutraceutical and environmental xenobiotics: an emerging role for xenobiotic-metabolizing enzymes and the transcription factors regulating their expression. A review". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 36 (2–3): 119–218. doi:10.1080/00498250600621627. PMID   16702112. S2CID   40503492.
  39. 1 2 Binder G, Wittekindt N, Ranke MB (February 2007). Noonan Syndrome: Genetics and Responsiveness to Growth Hormone Therapy. Vol. 67. pp. 45–49. doi:10.1159/000097552. ISBN   978-3-8055-8255-1. S2CID   84531041.{{cite book}}: |journal= ignored (help)
  40. ↑ "Actions of Anterior Pituitary Hormones: Physiologic Actions of GH". Medical College of Georgia. 2007. Archived from the original on 2008-01-11. Retrieved 2008-01-16.
  41. ↑ Ahmad A, Thomas J, Clewes A, Hokins MT, Guzder R, Ibrahim H, Durham B, Vora JP, Fraser WD (2003-06-01). "Effects of Growth Hormone Replacement on Parathyroid Hormone Sensitivity and Bone Mineral Metabolism". The Journal of Clinical Endocrinology & Metabolism. 88 (6): 2860–2868. doi: 10.1210/jc.2002-021787 . PMID   12788900.
  42. ↑ King MW (2006). "Structure and Function of Hormones: Growth Hormone". Indiana State University. Archived from the original on 2007-12-06. Retrieved 2008-01-16.
  43. ↑ T.F. Davies (ed.), A Case-Based Guide to Clinical Endocrinology, 2008, pag.16
  44. ↑ Sharma, Rita; Kopchick, John J.; Puri, Vishwajeet; Sharma, Vishva M. (2020-12-01). "Effect of Growth Hormone on Insulin Signaling". Molecular and Cellular Endocrinology. 518: 111038. doi:10.1016/j.mce.2020.111038. ISSN   0303-7207. PMC   7606590 . PMID   32966863.
  45. ↑ Artwelle G, Wislon FG (2008). New Human Growth Hormone Research. Nova Publishers. pp. 12–. ISBN   978-1-60456-438-9.
  46. ↑ "Norditropin® (somatropin) injection, for subcutaneous use" (PDF). Novo Nordisk A/S. U.S. Food and Drug Administration.
  47. ↑ Varlamov EV, McCartney S, Fleseriu M (April 2019). "Functioning Pituitary Adenomas - Current Treatment Options and Emerging Medical Therapies". European Endocrinology. 15 (1): 30–40. doi:10.17925/EE.2019.15.1.30. PMC   6587904 . PMID   31244908.
  48. 1 2 Ignatavicius D, Workman L (2015). Medical-Surgical Nursing: Patient-Centered Collaborative Care (8 ed.). Saunders. p. 1267. ISBN   978-1455772551.
  49. 1 2 3 Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Shalet SM, Vance ML, Stephens PA (May 2006). "Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology and Metabolism. 91 (5): 1621–34. doi: 10.1210/jc.2005-2227 . PMID   16636129.
  50. 1 2 Prodam F, Caputo M, Belcastro S, Garbaccio V, Zavattaro M, Samà MT, Bellone S, Pagano L, Bona G, Aimaretti G (December 2012). "Quality of life, mood disturbances and psychological parameters in adult patients with GH deficiency". Panminerva Medica. 54 (4): 323–31. PMID   23123585.
  51. 1 2 Nyberg F, Hallberg M (June 2013). "Growth hormone and cognitive function". Nature Reviews. Endocrinology. 9 (6): 357–65. doi:10.1038/nrendo.2013.78. PMID   23629538. S2CID   33876345.
  52. ↑ Dutta D, Mahajan K, Kumar M, Sharma M (Feb 2022). "Efficacy and safety of long-acting growth hormone in adult growth hormone deficiency: A systematic review and meta-analysis". Diabetes Metab Syndr. 16 (2): 102421. doi:10.1016/j.dsx.2022.102421. PMID   35158212. S2CID   246689650.
  53. ↑ "UpToDate". www.uptodate.com. Retrieved 2022-12-08.
  54. ↑ Gilden D (January 1995). "Human growth hormone available for AIDS wasting". GMHC Treatment Issues. 9 (1): 9–11. PMID   11367383.
  55. 1 2 DEA, US Department of Justice. DEA: Genotropin Archived 2015-04-04 at the Wayback Machine Quote: "The illicit distribution of hGH occurs as the result of physicians illegally prescribing it for off-label uses, and for the treatment of FDA-approved medical conditions without examination and supervision"
  56. ↑ Rudman D, Feller AG, Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF, Schlenker RA, Cohn L, Rudman IW, Mattson DE (July 1990). "Effects of human growth hormone in men over 60 years old". The New England Journal of Medicine. 323 (1): 1–6. doi: 10.1056/NEJM199007053230101 . PMID   2355952.
  57. 1 2 3 4 Liu H, Bravata DM, Olkin I, Nayak S, Roberts B, Garber AM, Hoffman AR (January 2007). "Systematic review: the safety and efficacy of growth hormone in the healthy elderly". Annals of Internal Medicine. 146 (2): 104–15. doi:10.7326/0003-4819-146-2-200701160-00005. PMID   17227934. S2CID   27279712.
  58. ↑ "No proof that growth hormone therapy makes you live longer, study finds". PhysOrg.com. 2007-01-16. Retrieved 2009-03-16.
  59. ↑ Kreidler M (June 5, 2016). "Growth Hormone Schemes and Scams | Quackwatch".
  60. ↑ Kuczynski A (1998-04-12). "Anti-Aging Potion or Poison?". New York Times.
  61. ↑ Mannfred A. Hollinger. Introduction to Pharmacology, Third Edition. CRC Press, 2002 ISBN   9780415280341 p. 376
  62. ↑ "21 U.S. Code § 333 – Penalties". LII / Legal Information Institute.
  63. ↑ Barclay L, Lie D (October 28, 2005). "Growth Hormone Deemed Illegal for Off-Label Antiaging Use". Medscape.
  64. ↑ Perls TT, Reisman NR, Olshansky SJ (October 2005). "Provision or distribution of growth hormone for "antiaging": clinical and legal issues". JAMA. 294 (16): 2086–90. doi:10.1001/jama.294.16.2086. PMID   16249424.
  65. 1 2 Caruso D, Donn J (December 21, 2012). "Big Pharma Cashes in on HGH Abuse". AP Impact. Associated Press. Archived from the original on August 12, 2014. Retrieved August 10, 2014.
  66. ↑ Edwards J (March 20, 2006). "Bad Medicine". BrandWeek. Archived from the original on 28 March 2006.
  67. 1 2 Zeman N (March 2012). "Hollywood's Vial Bodies". Vanity Fair.
  68. ↑ Freedman RJ, Malkovska V, LeRoith D, Collins MT (October 2005). "Hodgkin lymphoma in temporal association with growth hormone replacement". Endocrine Journal. 52 (5): 571–5. doi: 10.1507/endocrj.52.571 . PMID   16284435.
  69. ↑ Swerdlow AJ, Higgins CD, Adlard P, Preece MA (July 2002). "Risk of cancer in patients treated with human pituitary growth hormone in the UK, 1959-85: a cohort study". Lancet. 360 (9329): 273–7. doi:10.1016/S0140-6736(02)09519-3. PMID   12147369. S2CID   16216532.
  70. ↑ Holt RI, Erotokritou-Mulligan I, Sönksen PH (August 2009). "The history of doping and growth hormone abuse in sport". Growth Hormone & IGF Research. 19 (4): 320–6. doi:10.1016/j.ghir.2009.04.009. PMID   19467612.
  71. ↑ Liu H, Bravata DM, Olkin I, Friedlander A, Liu V, Roberts B, Bendavid E, Saynina O, Salpeter SR, Garber AM, Hoffman AR (May 2008). "Systematic review: the effects of growth hormone on athletic performance". Annals of Internal Medicine. 148 (10): 747–58. doi: 10.7326/0003-4819-148-10-200805200-00215 . PMID   18347346.
  72. ↑ Randall T (2008-03-17). "Athletes Don't Benefit From Human Growth Hormone, Study Finds". Bloomberg. Retrieved 2011-08-28.
  73. ↑ Gaffney G (2008-03-17). "Steroid Nation: Review from Stanford says HGH no benefit as PED". Steroid Nation. Retrieved 2011-08-28.
  74. ↑ Singleton ER (2010-06-04). "Atlas Operations, Inc". Warning Letter. U.S. Food and Drug Administration. Retrieved 2011-08-28.
  75. ↑ "Chicken from Farm to Table | USDA Food Safety and Inspection Service". Fsis.usda.gov. 2011-04-06. Archived from the original on 2011-09-03. Retrieved 2011-08-26.
  76. ↑ "Poultry Industry Frequently Asked Questions". U.S. Poultry & Egg Association. Retrieved June 21, 2012.
  77. ↑ "Hormones". Australian Chicken Meat Federation. Archived from the original on 1 July 2016. Retrieved 20 June 2016.
  78. ↑ "Center for Veterinary Medicine Master" (PDF). www.fda.gov. 2011-04-06. Retrieved 2011-08-28.
  79. ↑ Maybe NG (1984). "Direct expression of human growth in Escherichia coli with the lipoprotein promoter". In Bollon AP (ed.). Recombinant DNA products: insulin, interferon, and growth hormone. Boca Raton: CRC Press. ISBN   978-0-8493-5542-4.
  80. 1 2 Beck JC, Mcgarry EE, Dyrenfurth I, Venning EH (May 1957). "Metabolic effects of human and monkey growth hormone in man". Science. 125 (3253): 884–5. Bibcode:1957Sci...125..884B. doi:10.1126/science.125.3253.884. PMID   13421688.
  81. ↑ Beck JC, McGARRY EE, Dyrenfurth I, Venning EH (November 1958). "The metabolic effects of human and monkey growth hormone in man". Annals of Internal Medicine. 49 (5): 1090–105. doi:10.7326/0003-4819-49-5-1090. PMID   13595475.
  82. ↑ "FDA Response to three Citizen Petitions against biosimilars" (PDF), FDA, 30 May 2006, retrieved 23 November 2015
  83. ↑ In 2023, the FDA approved a different sustained-release form of growth hormone, Sogroya® (somapacitan-beco) (Novo) for both pediatric patients (2.5 years and older) and adult patients, whom have growth failure due to inadequate secretion of endogenous growth hormone (rHGH). Previously, the human growth hormone analog had only been approved for adult patients with growth hormone deficiency (AGHD). "Genentech and Alkermes Announce Decision to Discontinue Commercialization of Nutropin Depot". Press Release. Business Wire. 2004-06-01. Retrieved 2011-08-28.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.