Growth hormone

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"HGH" redirects here. Growth hormone_sentence_0

For other uses, see HGH (disambiguation). Growth hormone_sentence_1

Growth hormone_table_infobox_0

Growth hormone 1 (pituitary)Growth hormone_header_cell_0_0_0
IdentifiersGrowth hormone_header_cell_0_1_0
SymbolGrowth hormone_header_cell_0_2_0 GH1Growth hormone_cell_0_2_1
NCBI geneGrowth hormone_header_cell_0_3_0 Growth hormone_cell_0_3_1
HGNCGrowth hormone_header_cell_0_4_0 Growth hormone_cell_0_4_1
OMIMGrowth hormone_header_cell_0_5_0 Growth hormone_cell_0_5_1
RefSeqGrowth hormone_header_cell_0_6_0 Growth hormone_cell_0_6_1
UniProtGrowth hormone_header_cell_0_7_0 Growth hormone_cell_0_7_1
Other dataGrowth hormone_header_cell_0_8_0
LocusGrowth hormone_header_cell_0_9_0 Chr. 17Growth hormone_cell_0_9_1
Search forStructuresDomainsGrowth hormone_cell_0_10_0
Search forGrowth hormone_header_cell_0_11_0
StructuresGrowth hormone_header_cell_0_12_0 Growth hormone_cell_0_12_1
DomainsGrowth hormone_header_cell_0_13_0 Growth hormone_cell_0_13_1

Growth hormone_table_infobox_1

Growth hormone 2 (placental)Growth hormone_header_cell_1_0_0
IdentifiersGrowth hormone_header_cell_1_1_0
SymbolGrowth hormone_header_cell_1_2_0 GH2Growth hormone_cell_1_2_1
NCBI geneGrowth hormone_header_cell_1_3_0 Growth hormone_cell_1_3_1
HGNCGrowth hormone_header_cell_1_4_0 Growth hormone_cell_1_4_1
OMIMGrowth hormone_header_cell_1_5_0 Growth hormone_cell_1_5_1
RefSeqGrowth hormone_header_cell_1_6_0 Growth hormone_cell_1_6_1
UniProtGrowth hormone_header_cell_1_7_0 Growth hormone_cell_1_7_1
Other dataGrowth hormone_header_cell_1_8_0
LocusGrowth hormone_header_cell_1_9_0 Chr. 17Growth hormone_cell_1_9_1
Search forStructuresDomainsGrowth hormone_cell_1_10_0
Search forGrowth hormone_header_cell_1_11_0
StructuresGrowth hormone_header_cell_1_12_0 Growth hormone_cell_1_12_1
DomainsGrowth hormone_header_cell_1_13_0 Growth hormone_cell_1_13_1

Growth hormone (GH) or somatotropin, also known as human growth hormones (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. Growth hormone_sentence_2

It is thus important in human development. Growth hormone_sentence_3

GH also stimulates production of IGF-1 and increases the concentration of glucose and free fatty acids. Growth hormone_sentence_4

It is a type of mitogen which is specific only to the receptors on certain types of cells. Growth hormone_sentence_5

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. Growth hormone_sentence_6

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. Growth hormone_sentence_7

In the United States, it is only available legally from pharmacies by prescription from a licensed health care provider. Growth hormone_sentence_8

In recent years in the United States, some health care providers are prescribing growth hormone in the elderly to increase vitality. Growth hormone_sentence_9

While legal, the efficacy and safety of this use for HGH has not been tested in a clinical trial. Growth hormone_sentence_10

Many of the functions of hGH remain unknown. Growth hormone_sentence_11

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. Growth hormone_sentence_12

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. Growth hormone_sentence_13

Blood tests conducted by WADA at the 2004 Olympic Games in Athens, Greece targeted primarily HGH. Growth hormone_sentence_14

Use of the drug for performance enhancement is not currently approved by the FDA. Growth hormone_sentence_15

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. Growth hormone_sentence_16

These uses have been controversial. Growth hormone_sentence_17

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. Growth hormone_sentence_18

Retailers are permitted to label containers of milk as produced with or without bovine somatotropin. Growth hormone_sentence_19

Nomenclature Growth hormone_section_0

The names somatotropin (STH) or somatotropic hormone refer to the growth hormone produced naturally in animals and extracted from carcasses. Growth hormone_sentence_20

Hormone extracted from human cadavers is abbreviated hGH. Growth hormone_sentence_21

The main growth hormone produced by recombinant DNA technology has the approved generic name (INN) somatropin and the brand name Humatrope, and is properly abbreviated rhGH in the scientific literature. Growth hormone_sentence_22

Since its introduction in 1992 Humatrope has been a banned sports doping agent, and in this context is referred to as HGH. Growth hormone_sentence_23

Biology Growth hormone_section_1

Gene Growth hormone_section_2

Main articles: Growth hormone 1 and Growth hormone 2 Growth hormone_sentence_24

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 and are closely related to human chorionic somatomammotropin (also known as placental lactogen) genes. Growth hormone_sentence_25

GH, human chorionic somatomammotropin, and prolactin belong to a group of homologous hormones with growth-promoting and lactogenic activity. Growth hormone_sentence_26

Structure Growth hormone_section_3

The major isoform of the human growth hormone is a protein of 191 amino acids and a molecular weight of 22,124 daltons. Growth hormone_sentence_27

The structure includes four helices necessary for functional interaction with the GH receptor. Growth hormone_sentence_28

It appears that, in structure, GH is evolutionarily homologous to prolactin and chorionic somatomammotropin. Growth hormone_sentence_29

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. Growth hormone_sentence_30

Several molecular isoforms of GH exist in the pituitary gland and are released to blood. Growth hormone_sentence_31

In particular, a variant of approximately 20 kDa originated by an alternative splicing is present in a rather constant 1:9 ratio, while recently an additional variant of ~ 23-24 kDa has also been reported in post-exercise states at higher proportions. Growth hormone_sentence_32

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. Growth hormone_sentence_33

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). Growth hormone_sentence_34

Regulation Growth hormone_section_4

See also: Hypothalamic–pituitary–somatotropic axis Growth hormone_sentence_35

Secretion of growth hormone (GH) in the pituitary is regulated by the neurosecretory nuclei of the hypothalamus. Growth hormone_sentence_36

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. Growth hormone_sentence_37

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. Growth hormone_sentence_38

Somatotropic cells in the anterior pituitary gland then synthesize and secrete GH in a pulsatile manner, in response to these stimuli by the hypothalamus. Growth hormone_sentence_39

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. Growth hormone_sentence_40

Otherwise there is wide variation between days and individuals. Growth hormone_sentence_41

Nearly fifty percent of GH secretion occurs during the third and fourth NREM sleep stages. Growth hormone_sentence_42

Surges of secretion during the day occur at 3- to 5-hour intervals. Growth hormone_sentence_43

The plasma concentration of GH during these peaks may range from 5 to even 45 ng/mL. Growth hormone_sentence_44

Between the peaks, basal GH levels are low, usually less than 5 ng/mL for most of the day and night. Growth hormone_sentence_45

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. Growth hormone_sentence_46

A number of factors are known to affect GH secretion, such as age, sex, diet, exercise, stress, and other hormones. Growth hormone_sentence_47

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. Growth hormone_sentence_48

Sleep deprivation generally suppresses GH release, particularly after early adulthood. Growth hormone_sentence_49

Stimulators of growth hormone (GH) secretion include: Growth hormone_sentence_50

Growth hormone_unordered_list_0

  • Peptide hormonesGrowth hormone_item_0_0
    • GHRH (somatocrinin) through binding to the growth hormone-releasing hormone receptor (GHRHR)Growth hormone_item_0_1
    • Ghrelin through binding to growth hormone secretagogue receptors (GHSR)Growth hormone_item_0_2
  • Sex hormonesGrowth hormone_item_0_3
    • Increased androgen secretion during puberty (in males from testes and in females from adrenal cortex)Growth hormone_item_0_4
    • Testosterone and DHEAGrowth hormone_item_0_5
    • EstrogenGrowth hormone_item_0_6
  • Clonidine and L-DOPA by stimulating GHRH releaseGrowth hormone_item_0_7
  • α4β2 nicotinic agonists, including nicotine, which also act synergistically with clonidine.Growth hormone_item_0_8
  • Hypoglycemia, arginine and propranolol by inhibiting somatostatin releaseGrowth hormone_item_0_9
  • Deep sleepGrowth hormone_item_0_10
  • InsulinGrowth hormone_item_0_11
  • GlucagonGrowth hormone_item_0_12
  • Niacin as nicotinic acid (vitamin B3)Growth hormone_item_0_13
  • FastingGrowth hormone_item_0_14
  • Vigorous exerciseGrowth hormone_item_0_15

Inhibitors of GH secretion include: Growth hormone_sentence_51

Growth hormone_unordered_list_1

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. Growth hormone_sentence_52

Function Growth hormone_section_5

Effects of growth hormone on the tissues of the body can generally be described as anabolic (building up). Growth hormone_sentence_53

Like most other protein hormones, GH acts by interacting with a specific receptor on the surface of cells. Growth hormone_sentence_54

Increased height during childhood is the most widely known effect of GH. Growth hormone_sentence_55

Height appears to be stimulated by at least two mechanisms: Growth hormone_sentence_56

Growth hormone_ordered_list_2

  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. Through this mechanism GH directly stimulates division and multiplication of chondrocytes of cartilage.Growth hormone_item_2_22
  2. GH also stimulates, through the JAK-STAT signaling pathway, the production of insulin-like growth factor 1 (IGF-1, formerly known as somatomedin C), a hormone homologous to proinsulin. 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.Growth hormone_item_2_23

In addition to increasing height in children and adolescents, growth hormone has many other effects on the body: Growth hormone_sentence_57

Growth hormone_unordered_list_3

Biochemistry Growth hormone_section_6

GH has a short biological half-life of about 10 to 20 minutes. Growth hormone_sentence_58

Clinical significance Growth hormone_section_7

Excess Growth hormone_section_8

The most common disease of GH excess is a pituitary tumor composed of somatotroph cells of the anterior pituitary. Growth hormone_sentence_59

These somatotroph adenomas are benign and grow slowly, gradually producing more and more GH. Growth hormone_sentence_60

For years, the principal clinical problems are those of GH excess. Growth hormone_sentence_61

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. Growth hormone_sentence_62

Prolonged GH excess thickens the bones of the jaw, fingers and toes, resulting heaviness of the jaw and increased size of digits, referred to as acromegaly. Growth hormone_sentence_63

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. Growth hormone_sentence_64

GH-secreting tumors are typically recognized in the fifth decade of life. Growth hormone_sentence_65

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. Growth hormone_sentence_66

Surgical removal is the usual treatment for GH-producing tumors. Growth hormone_sentence_67

In some circumstances, focused radiation or a GH antagonist such as pegvisomant may be employed to shrink the tumor or block function. Growth hormone_sentence_68

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. Growth hormone_sentence_69

Deficiency Growth hormone_section_9

Main article: Growth hormone deficiency Growth hormone_sentence_70

The effects of growth hormone (GH) deficiency vary depending on the age at which they occur. Growth hormone_sentence_71

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. Growth hormone_sentence_72

Major manifestations of GH deficiency in children are growth failure, the development of a short stature, and delayed sexual maturity. Growth hormone_sentence_73

In adults, somatomedin alteration contributes to increased osteoclast activity, resulting in weaker bones that are more prone to pathologic fracture and osteoporosis. Growth hormone_sentence_74

However, deficiency is rare in adults, with the most common cause being a pituitary adenoma. Growth hormone_sentence_75

Other adult causes include a continuation of a childhood problem, other structural lesions or trauma, and very rarely idiopathic GHD. Growth hormone_sentence_76

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". Growth hormone_sentence_77

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. Growth hormone_sentence_78

Psychological effects Growth hormone_section_10

Quality of life Growth hormone_section_11

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. Growth hormone_sentence_79

Adults with GH deficiency often have higher rates of depression than those without. Growth hormone_sentence_80

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. Growth hormone_sentence_81

Cognitive function Growth hormone_section_12

GH has also been studied in the context of cognitive function, including learning and memory. Growth hormone_sentence_82

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. Growth hormone_sentence_83

Medical uses Growth hormone_section_13

Main article: Growth hormone therapy Growth hormone_sentence_84

Replacement therapy Growth hormone_section_14

Treatment with exogenous GH is indicated only in limited circumstances, and needs regular monitoring due to the frequency and severity of side-effects. Growth hormone_sentence_85

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). Growth hormone_sentence_86

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. Growth hormone_sentence_87

Other approved uses Growth hormone_section_15

GH can be used to treat conditions that produce short stature but are not related to deficiencies in GH. Growth hormone_sentence_88

However, results are not as dramatic when compared to short stature that is solely attributable to deficiency of GH. Growth hormone_sentence_89

Examples of other causes of shortness often treated with GH are Turner syndrome, chronic kidney failure, Prader–Willi syndrome, intrauterine growth restriction, and severe idiopathic short stature. Growth hormone_sentence_90

Higher ("pharmacologic") doses are required to produce significant acceleration of growth in these conditions, producing blood levels well above normal ("physiologic"). Growth hormone_sentence_91

Despite the higher doses, side-effects during treatment are rare, and vary little according to the condition being treated. Growth hormone_sentence_92

One version of rHGH has also been FDA approved for maintaining muscle mass in wasting due to AIDS. Growth hormone_sentence_93

Off-label use Growth hormone_section_16

Main article: HGH controversies Growth hormone_sentence_94

Off-label prescription of HGH is controversial and may be illegal. Growth hormone_sentence_95

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. Growth hormone_sentence_96

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. Growth hormone_sentence_97

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. Growth hormone_sentence_98

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. Growth hormone_sentence_99

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". Growth hormone_sentence_100

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. Growth hormone_sentence_101

However, these were the only positive effects from taking GH. Growth hormone_sentence_102

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. Growth hormone_sentence_103

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. Growth hormone_sentence_104

This would explain the increase in lean body mass. Growth hormone_sentence_105

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. Growth hormone_sentence_106

GH has also been used experimentally in patients with short bowel syndrome to lessen the requirement for intravenous total parenteral nutrition. Growth hormone_sentence_107

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. Growth hormone_sentence_108

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. Growth hormone_sentence_109

This section has also been interpreted by some doctors, most notably 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. Growth hormone_sentence_110

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. Growth hormone_sentence_111

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." Growth hormone_sentence_112

At the same time, anti-aging clinics where doctors prescribe, administer, and sell HGH to people are big business. Growth hormone_sentence_113

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. Growth hormone_sentence_114

doesn't regulate off-label uses of H.G.H. Growth hormone_sentence_115

Sometimes it's used appropriately. Growth hormone_sentence_116

Sometimes it's not." Growth hormone_sentence_117

Side effects Growth hormone_section_17

Injection-site reaction is common. Growth hormone_sentence_118

More rarely, patients can experience joint swelling, joint pain, carpal tunnel syndrome, and an increased risk of diabetes. Growth hormone_sentence_119

In some cases, the patient can produce an immune response against GH. Growth hormone_sentence_120

GH may also be a risk factor for Hodgkin's lymphoma. Growth hormone_sentence_121

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. Growth hormone_sentence_122

Performance enhancement Growth hormone_section_18

Main article: Growth hormone in sports Growth hormone_sentence_123

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. Growth hormone_sentence_124

Athletes in many sports have used human growth hormone in order to attempt to enhance their athletic performance. Growth hormone_sentence_125

Some recent studies have not been able to support claims that human growth hormone can improve the athletic performance of professional male athletes. Growth hormone_sentence_126

Many athletic societies ban the use of GH and will issue sanctions against athletes who are caught using it. Growth hormone_sentence_127

However, because GH is a potent endogenous protein, it is very difficult to detect GH doping. Growth hormone_sentence_128

In the United States, GH is legally available only by prescription from a medical doctor. Growth hormone_sentence_129

Dietary supplements Growth hormone_section_19

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". Growth hormone_sentence_130

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. Growth hormone_sentence_131

In the United States, because these products are marketed as dietary supplements, it is illegal for them to contain GH, which is a drug. Growth hormone_sentence_132

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. Growth hormone_sentence_133

The FTC and the FDA do enforce the law when they become aware of violations. Growth hormone_sentence_134

Agricultural use Growth hormone_section_20

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. Growth hormone_sentence_135

The use of GH in poultry farming is illegal in the United States. Growth hormone_sentence_136

Similarly, no chicken meat for sale in Australia is administered hormones. Growth hormone_sentence_137

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. Growth hormone_sentence_138

Drug development history Growth hormone_section_21

Main article: Growth hormone treatment § History Growth hormone_sentence_139

The identification, purification and later synthesis of growth hormone is associated with Choh Hao Li. Growth hormone_sentence_140

Genentech pioneered the first use of recombinant human growth hormone for human therapy in 1981. Growth hormone_sentence_141

Prior to its production by recombinant DNA technology, growth hormone used to treat deficiencies was extracted from the pituitary glands of cadavers. Growth hormone_sentence_142

Attempts to create a wholly synthetic HGH failed. Growth hormone_sentence_143

Limited supplies of HGH resulted in the restriction of HGH therapy to the treatment of idiopathic short stature. Growth hormone_sentence_144

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. Growth hormone_sentence_145

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. Growth hormone_sentence_146

... Growth hormone_sentence_147

There was a gain in body weight during both periods. Growth hormone_sentence_148

... Growth hormone_sentence_149

There was a significant increase in urinary excretion of aldosterone during both periods of administration of growth hormone. Growth hormone_sentence_150

This was most marked with the human growth hormone. Growth hormone_sentence_151

... Impairment of the glucose tolerance curve was evident after 10 days of administration of the human growth hormone. Growth hormone_sentence_152

No change in glucose tolerance was demonstrable on the fifth day of administration of monkey growth hormone." Growth hormone_sentence_153

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. Growth hormone_sentence_154

In 1985, unusual cases of Creutzfeldt–Jakob disease were found in individuals that had received cadaver-derived HGH ten to fifteen years previously. Growth hormone_sentence_155

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. Growth hormone_sentence_156

In 1985, biosynthetic human growth hormone replaced pituitary-derived human growth hormone for therapeutic use in the U.S. and elsewhere. Growth hormone_sentence_157

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). Growth hormone_sentence_158

In 2006, the U.S. Food and Drug Administration (FDA) approved a version of rHGH called Omnitrope (Sandoz). Growth hormone_sentence_159

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). Growth hormone_sentence_160

See also Growth hormone_section_22

Growth hormone_unordered_list_4

Credits to the contents of this page go to the authors of the corresponding Wikipedia page: hormone.