View source for Growth hormone

{{Redirect|HGH}}
{{Infobox protein
| Name = [[Growth hormone 1]]
| caption = Growth hormone
| image = Somatotropine.GIF
| width = 240
| HGNCid = 4261
| Symbol = [[Growth hormone 1|GH1]]
| AltSymbols =
| EntrezGene = 2688
| OMIM = 139250
| RefSeq = NM_022562
| UniProt = P01241
| PDB =
| ECnumber =
| Chromosome = 17
| Arm = q
| Band = 22
| LocusSupplementaryData = -q24
}}
{{Infobox protein
| Name = [[Growth hormone 2]]
| caption =
| image =
| width =
| HGNCid = 4262
| Symbol = [[Growth hormone 2|GH2]]
| AltSymbols =
| EntrezGene = 2689
| OMIM = 139240
| RefSeq = NM_002059
| UniProt = P01242
| PDB =
| ECnumber =
| Chromosome = 17
| Arm = q
| Band = 22
| LocusSupplementaryData = -q24
}}

'''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 (biology)|cell]] reproduction, and cell regeneration in humans and other animals. It is thus important in [[human development (biology)|human development]]. It is a type of [[mitogen]] which is specific only to certain kinds of cells. Growth hormone is a 191-[[amino acid]], single-chain [[polypeptide]] that is synthesized, stored and secreted by [[somatotropic cell]]s within the lateral wings of the [[anterior pituitary]] gland.

GH is a stress hormone that stimulates production of [[IGF-1]] and raises the concentration of glucose and free fatty acids.<ref name="pmid21584161">{{cite journal | vauthors = Ranabir S, Reetu K | title = Stress and hormones | journal = Indian Journal of Endocrinology and Metabolism | volume = 15 | issue = 1 | pages = 18–22 | date = January 2011 | pmid = 21584161 | pmc = 3079864 | doi = 10.4103/2230-8210.77573 }}</ref><ref name="pmid5960526">{{cite journal | vauthors = Greenwood FC, Landon J | title = Growth hormone secretion in response to stress in man | journal = Nature | volume = 210 | issue = 5035 | pages = 540–1 | date = April 1966 | pmid = 5960526 | doi = 10.1038/210540a0 }}</ref>  

A [[recombinant DNA|recombinant]] form of hGH called '''somatropin''' ([[International Nonproprietary Name|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 doctor. In recent years in the United States, some doctors have started to prescribe growth hormone in GH-deficient older patients (but not on healthy people) to increase vitality.   While legal, the efficacy and safety of this use for HGH has not been tested in a clinical trial.   At this time, HGH is still considered a very complex hormone, and many of its functions are still unknown.<ref name="ped">{{cite book | author = Powers M |veditors=Leaver-Dunn D, Houglum J, Harrelson GL | title = Principles of Pharmacology for Athletic Trainers | edition = | publisher = Slack Incorporated | location = | year = 2005 | origyear = | pages = 331–332 | chapter = Performance-Enhancing Drugs| quote = | isbn = 1-55642-594-5 }}</ref>

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 [[Use of performance-enhancing drugs in sport|doping]] with HGH, so the ban was unenforceable until the early 2000s, when [[blood test]]s that could distinguish between natural and artificial HGH were starting to be developed. Blood tests conducted by [[World Anti-Doping Agency|WADA]] at the [[2004 Olympic Games]] in [[Athens, Greece]] targeted primarily HGH.<ref name=ped/>  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 1|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 ([[International Nonproprietary Name|INN]]) ''somatropin'' and the brand name ''Humatrope'',<ref>{{cite journal | vauthors = Daniels ME | title= Lilly's Humatrope Experience | journal = Nature Biotechnology | volume = 10 | pages = 812 | year = 1992 | doi = 10.1038/nbt0792-812a | issue=7}}</ref> and is properly abbreviated rhGH in the scientific literature. Since its introduction in 1992 Humatrope has been a banned sports doping agent,<ref name="pmid16799101">{{cite journal | vauthors = Saugy M, Robinson N, Saudan C, Baume N, Avois L, Mangin P | title = Human growth hormone doping in sport | journal = British Journal of Sports Medicine | volume = 40 Suppl 1 | issue =  | pages = i35-9 | date = July 2006 | pmid = 16799101 | pmc = 2657499 | doi = 10.1136/bjsm.2006.027573 }}</ref> and in this context is referred to as HGH.

==Biology==

===Gene===
{{Main|Growth hormone 1|Growth hormone 2}}
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<ref name="urlGH1 growth hormone 1 (Homo sapiens) - Gene - NCBI">{{cite web | url = https://www.ncbi.nlm.nih.gov/gene/2688 | title = GH1 growth hormone 1 (Homo sapiens) - Gene  | publisher = National Center for Biotechnology Information, U.S. National Library of Medicine }}</ref><ref name="urlGH2 growth hormone 2 (Homo sapiens) - Gene - NCBI">{{cite web | url = https://www.ncbi.nlm.nih.gov/gene/2689 | title = GH2 growth hormone 2 (Homo sapiens) - Gene | publisher = National Center for Biotechnology Information, U.S. National Library of Medicine }}</ref> and are closely related to [[somatomammotropin|human chorionic somatomammotropin]] (also known as [[placental lactogen]]) genes. GH, human chorionic somatomammotropin, and [[prolactin]] belong to [[Somatotropin family|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 acid]]s and a molecular weight of 22,124 [[Atomic mass unit|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]].<ref name="pmid12082127">{{cite journal | vauthors = Yi S, Bernat B, Pál G, Kossiakoff A, Li WH | title = Functional promiscuity of squirrel monkey growth hormone receptor toward both primate and nonprimate growth hormones | journal = Molecular Biology and Evolution | volume = 19 | issue = 7 | pages = 1083–92 | date = July 2002 | pmid = 12082127 | doi = 10.1093/oxfordjournals.molbev.a004166 }}</ref>

Several [[molecule|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,<ref name="pmid12217902">{{cite journal | vauthors = Leung KC, Howe C, Gui LY, Trout G, Veldhuis JD, Ho KK | title = Physiological and pharmacological regulation of 20-kDa growth hormone | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 283 | issue = 4 | pages = E836-43 | date = October 2002 | pmid = 12217902 | doi = 10.1152/ajpendo.00122.2002 }}</ref> while recently an additional variant of ~ 23-24 kDa has also been reported in post-exercise states at higher proportions.<ref name="pmid19003817">{{cite journal | vauthors = Kohler M, Püschel K, Sakharov D, Tonevitskiy A, Schänzer W, Thevis M | title = Detection of recombinant growth hormone in human plasma by a 2-D PAGE method | journal = Electrophoresis | volume = 29 | issue = 22 | pages = 4495–502 | date = November 2008 | pmid = 19003817 | doi = 10.1002/elps.200800221 }}</ref> 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.<ref name="pmid19579232">{{cite journal | vauthors = Bustamante JJ, Gonzalez L, Carroll CA, Weintraub ST, Aguilar RM, Muñoz J, Martinez AO, Haro LS | title = O-Glycosylated 24 kDa human growth hormone has a mucin-like biantennary disialylated tetrasaccharide attached at Thr-60 | journal = Proteomics | volume = 9 | issue = 13 | pages = 3474–88 | date = July 2009 | pmid = 19579232 | pmc = 2904392 | doi = 10.1002/pmic.200800989 }}</ref> 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===
{{See also|Hypothalamic–pituitary–somatotropic axis}}

Secretion of growth hormone (GH) in the pituitary is regulated by the [[Neurosecretion|neurosecretory]] nuclei of the [[hypothalamus]]. 
These cells release the peptides [[Growth hormone-releasing hormone]] (GHRH or ''somatocrinin'') and [[Somatostatin|Growth hormone-inhibiting hormone]] (GHIH or ''somatostatin'') into the [[hypophyseal portal system|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.<ref name="isbn0-321-53910-9">{{cite book |vauthors=Bartholomew EF, Martini F, Nath JL | title = Fundamentals of anatomy & physiology | edition = | publisher = Pearson Education Inc | location = Upper Saddle River, NJ | year = 2009 | origyear = | pages = 616–617 | quote = | isbn = 0-321-53910-9 }}</ref>

[[Somatotropic cell]]s 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&nbsp;ng/mL.<ref name="Takahashi">{{cite journal | vauthors = Takahashi Y, Kipnis DM, Daughaday WH | title = Growth hormone secretion during sleep | journal = The Journal of Clinical Investigation | volume = 47 | issue = 9 | pages = 2079–90 | date = September 1968 | pmid = 5675428 | pmc = 297368 | doi = 10.1172/JCI105893 }}</ref> 
Otherwise there is wide variation between days and individuals. Nearly fifty percent of GH secretion occurs during the third and fourth [[NREM sleep]] stages.<ref name="pmid11817985">{{cite journal | vauthors = Mehta A, Hindmarsh PC | title = The use of somatropin (recombinant growth hormone) in children of short stature | journal = Paediatric Drugs | volume = 4 | issue = 1 | pages = 37–47 | year = 2002 | pmid = 11817985 | doi = 10.2165/00128072-200204010-00005 }}</ref>
Surges of secretion during the day occur at 3- to 5-hour intervals.<ref name=ped/> The plasma concentration of GH during these peaks may range from 5 to even 45&nbsp;ng/mL.<ref name="pmid808970">{{cite journal | vauthors = Natelson BH, Holaday J, Meyerhoff J, Stokes PE | title = Temporal changes in growth hormone, cortisol, and glucose: relation to light onset and behavior | journal = The American Journal of Physiology | volume = 229 | issue = 2 | pages = 409–15 | date = August 1975 | pmid = 808970 | doi = 10.1152/ajplegacy.1975.229.2.409 | url = http://ajplegacy.physiology.org/cgi/content/abstract/229/2/409 }}</ref>
Between the peaks, basal GH levels are low, usually less than 5&nbsp;ng/mL for most of the day and night.<ref name="Takahashi"/> Additional analysis of the pulsatile profile of GH described in all cases less than 1&nbsp;ng/ml for basal levels while maximum peaks were situated around 10-20&nbsp;ng/mL.<ref name="pmid11408427">{{cite journal | vauthors = Nindl BC, Hymer WC, Deaver DR, Kraemer WJ | title = Growth hormone pulsatility profile characteristics following acute heavy resistance exercise | journal = Journal of Applied Physiology | volume = 91 | issue = 1 | pages = 163–72 | date = July 2001 | pmid = 11408427 | doi = 10.1152/jappl.2001.91.1.163 | url = http://jap.physiology.org/cgi/content/abstract/91/1/163 }}</ref><ref name="pmid8719443">{{cite journal | vauthors = Juul A, Jørgensen JO, Christiansen JS, Müller J, Skakkeboek NE | title = Metabolic effects of GH: a rationale for continued GH treatment of GH-deficient adults after cessation of linear growth | journal = Hormone Research | volume = 44 Suppl 3 | issue = 3 | pages = 64–72 | year = 1995 | pmid = 8719443 | doi = 10.1159/000184676 }}</ref>

A number of factors are known to affect GH secretion, such as age, sex, diet, exercise, stress, and other hormones.<ref name=ped/> 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.<ref name = "isbn0-07-144011-9" >{{cite book |vauthors=Gardner DG, Shoback D | title = Greenspan's Basic and Clinical Endocrinology | edition = 8th |series= | year = 2007 | publisher= McGraw-Hill Medical | location = New York | isbn = 0-07-144011-9 |oclc= | pages = 193–201 | chapter = | chapterurl = | quote = }}</ref> Sleep deprivation generally suppresses GH release, particularly after early adulthood.<ref name="pmid8875441">{{cite journal | vauthors = Mullington J, Hermann D, Holsboer F, Pollmächer T | title = Age-dependent suppression of nocturnal growth hormone levels during sleep deprivation | journal = Neuroendocrinology | volume = 64 | issue = 3 | pages = 233–41 | date = September 1996 | pmid = 8875441 | doi = 10.1159/000127122 }}</ref>

Stimulators of growth hormone (GH) secretion include:
* peptide hormones
** [[Growth hormone–releasing hormone|GHRH]] (''somatocrinin'') through binding to the growth hormone-releasing hormone receptor ([[growth hormone releasing hormone receptor|GHRHR]])<ref name="pmid12424433">{{cite journal | vauthors = Lin-Su K, Wajnrajch MP | title = Growth Hormone Releasing Hormone (GHRH) and the GHRH Receptor | journal = Reviews in Endocrine & Metabolic Disorders | volume = 3 | issue = 4 | pages = 313–23 | date = December 2002 | pmid = 12424433 | doi = 10.1023/A:1020949507265 }}</ref>
** [[ghrelin]] through binding to growth hormone secretagogue receptors ([[growth hormone secretagogue receptor|GHSR]])<ref name="pmid11089570">{{cite journal | vauthors = Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DG, Ghatei MA, Bloom SR | title = The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion | journal = Endocrinology | volume = 141 | issue = 11 | pages = 4325–8 | date = November 2000 | pmid = 11089570 | doi = 10.1210/endo.141.11.7873 }}</ref>
* sex hormones<ref name="pmid16984231">{{cite journal | vauthors = Meinhardt UJ, Ho KK | title = Modulation of growth hormone action by sex steroids | journal = Clinical Endocrinology | volume = 65 | issue = 4 | pages = 413–22 | date = October 2006 | pmid = 16984231 | doi = 10.1111/j.1365-2265.2006.02676.x }}</ref>
** increased [[androgen]] secretion during puberty (in males from testes and in females from adrenal cortex)
** [[estrogen]]
* [[clonidine]] and [[L-DOPA]] by stimulating GHRH release<ref name="pmid1901390">{{cite journal | vauthors = Low LC | title = Growth hormone-releasing hormone: clinical studies and therapeutic aspects | journal = Neuroendocrinology | volume = 53 Suppl 1 | issue =  | pages = 37–40 | year = 1991 | pmid = 1901390 | doi = 10.1159/000125793 }}</ref>
* [[Alpha-4 beta-2 nicotinic receptor#Agonists|α4β2 nicotinic agonists]], including [[nicotine]], which also act synergistically with [[clonidine]].<ref name="pmid18042647">{{cite journal | vauthors = Fedi M, Bach LA, Berkovic SF, Willoughby JO, Scheffer IE, Reutens DC | title = Association of a nicotinic receptor mutation with reduced height and blunted physostigmine-stimulated growth hormone release | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 93 | issue = 2 | pages = 634–7 | date = February 2008 | pmid = 18042647 | doi = 10.1210/jc.2007-1611 }}</ref><ref name="pmid6818588">{{cite journal | vauthors = Wilkins JN, Carlson HE, Van Vunakis H, Hill MA, Gritz E, Jarvik ME | title = Nicotine from cigarette smoking increases circulating levels of cortisol, growth hormone, and prolactin in male chronic smokers | journal = Psychopharmacology | volume = 78 | issue = 4 | pages = 305–8 | year = 1982 | pmid = 6818588 | doi = 10.1007/BF00433730 }}</ref><ref name="pmid6508989">{{cite journal | vauthors = Coiro V, d'Amato L, Borciani E, Rossi G, Camellini L, Maffei ML, Pignatti D, Chiodera P | title = Nicotine from cigarette smoking enhances clonidine-induced increase of serum growth hormone concentrations in men | journal = British Journal of Clinical Pharmacology | volume = 18 | issue = 5 | pages = 802–5 | date = November 1984 | pmid = 6508989 | pmc = 1463553 | doi = 10.1111/j.1365-2125.1984.tb02547.x }}</ref>
* [[hypoglycemia]], [[arginine]]<ref name="pmid2903866">{{cite journal | vauthors = Alba-Roth J, Müller OA, Schopohl J, von Werder K | title = Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 67 | issue = 6 | pages = 1186–9 | date = December 1988 | pmid = 2903866 | doi = 10.1210/jcem-67-6-1186 }}</ref> and [[propranolol]] by inhibiting [[somatostatin]] release<ref name="pmid1901390" />
* [[deep sleep]]<ref name="pmid15135771">{{cite journal | vauthors = Van Cauter E, Latta F, Nedeltcheva A, Spiegel K, Leproult R, Vandenbril C, Weiss R, Mockel J, Legros JJ, Copinschi G | title = Reciprocal interactions between the GH axis and sleep | journal = Growth Hormone & IGF Research | volume = 14 Suppl A | issue =  | pages = S10-7 | date = June 2004 | pmid = 15135771 | doi = 10.1016/j.ghir.2004.03.006 }}</ref>
* [[niacin]] as nicotinic acid (Vitamin B3)<ref name="pmid6345570">{{cite journal | vauthors = Quabbe HJ, Luyckx AS, L'age M, Schwarz C | title = Growth hormone, cortisol, and glucagon concentrations during plasma free fatty acid depression: different effects of nicotinic acid and an adenosine derivative (BM 11.189) | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 57 | issue = 2 | pages = 410–4 | date = August 1983 | pmid = 6345570 | doi = 10.1210/jcem-57-2-410 }}</ref>
* [[fasting]]<ref name="pmid15809014">{{cite journal | vauthors = Nørrelund H | title = The metabolic role of growth hormone in humans with particular reference to fasting | journal = Growth Hormone & IGF Research | volume = 15 | issue = 2 | pages = 95–122 | date = April 2005 | pmid = 15809014 | doi = 10.1016/j.ghir.2005.02.005 }}</ref>
* vigorous [[exercise]] <ref name="pmid9375348">{{cite journal | vauthors = Kanaley JA, Weltman JY, Veldhuis JD, Rogol AD, Hartman ML, Weltman A | title = Human growth hormone response to repeated bouts of aerobic exercise | journal = Journal of Applied Physiology | volume = 83 | issue = 5 | pages = 1756–61 | date = November 1997 | pmid = 9375348 | doi = 10.1152/jappl.1997.83.5.1756 | url = http://jap.physiology.org/cgi/content/full/83/5/1756 }}</ref>

''Inhibitors'' of GH secretion include:
* [[Somatostatin|GHIH]] (''somatostatin'') from the [[periventricular nucleus]]  <ref name="pmid779605">{{cite journal | vauthors = Guillemin R, Gerich JE | title = Somatostatin: physiological and clinical significance | journal = Annual Review of Medicine | volume = 27 | issue =  | pages = 379–88 | year = 1976 | pmid = 779605 | doi = 10.1146/annurev.me.27.020176.002115 }}</ref>
* circulating concentrations of GH and [[IGF-1]] ([[negative feedback]] on the pituitary and [[hypothalamus]])<ref name=ped/>
* [[hyperglycemia]]<ref name="pmid1901390" />
* [[glucocorticoid]]s<ref name="pmid8879994">{{cite journal | vauthors = Allen DB | title = Growth suppression by glucocorticoid therapy | journal = Endocrinology and Metabolism Clinics of North America | volume = 25 | issue = 3 | pages = 699–717 | date = September 1996 | pmid = 8879994 | doi = 10.1016/S0889-8529(05)70348-0 }}</ref>
* [[dihydrotestosterone]]

In addition to control by endogenous and stimulus processes, a number of foreign compounds ([[xenobiotic]]s such as drugs and [[endocrine disruptor]]s) are known to influence GH secretion and function.<ref name="pmid16702112">{{cite journal | vauthors = Scarth JP | title = 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 | journal = Xenobiotica; The Fate of Foreign Compounds in Biological Systems | volume = 36 | issue = 2-3 | pages = 119–218 | year = 2006 | pmid = 16702112 | doi = 10.1080/00498250600621627 }}</ref>

=== Function ===
[[File:Endocrine growth regulation.svg|thumb|240px|Main pathways in endocrine regulation of growth]]

Effects of growth hormone on the tissues of the body can generally be described as [[anabolism|anabolic]] (building up).  Like most other protein hormones, GH acts by interacting with a specific [[receptor (biochemistry)|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:

# 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]].<ref name="Binder_2007">{{cite journal |vauthors=Binder G, Wittekindt N, Ranke MB | title = Noonan Syndrome: Genetics and Responsiveness to Growth Hormone Therapy | journal = Horm Res |date=February 2007 | volume = 67 | isbn = 978-3-8055-8255-1 | issue = Supplement 1 | pages = 45–49 | doi=10.1159/000097552 | url = https://books.google.com/?id=nQ9ilbixQEgC&pg=PA46&lpg=PA46&dq=gh+growth+hormone+ras&q=gh%20growth%20hormone%20ras}}</ref> Through this mechanism GH directly stimulates division and multiplication of [[chondrocyte]]s of [[cartilage]].
# GH also stimulates, through the [[JAK-STAT signaling pathway]],<ref name="Binder_2007"/> the production of [[insulin-like growth factor 1]] (IGF-1, formerly known as somatomedin C), a hormone homologous to [[proinsulin]].<ref>{{cite web | url = http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch2/s5ch2_19.htm | title = Actions of Anterior Pituitary Hormones: Physiologic Actions of GH | publisher = Medical College of Georgia | year = 2007 | access-date = 2008-01-16 | deadurl = yes | archive-url = https://web.archive.org/web/20080111163402/http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch2/s5ch2_19.htm | archive-date = 2008-01-11 | df =  }}</ref> 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 gland|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:
* Increases [[calcium]] retention,{{Citation needed|date=October 2015}} and strengthens and increases the [[mineralization of bone]]
* Increases [[muscle]] mass through [[sarcomere]] [[hypertrophy]]
* Promotes [[lipolysis]]
* Increases [[protein synthesis]]
* Stimulates the growth of all internal organs excluding the [[brain]]
* Plays a role in [[homeostasis]]
* Reduces [[liver]] uptake of [[glucose]]
* Promotes [[gluconeogenesis]] in the liver<ref>{{cite web | author  = King MW | url = http://web.indstate.edu/thcme/mwking/peptide-hormones.html#gh | title = Structure and Function of Hormones:  Growth Hormone | publisher = [[Indiana State University]] | year = 2006 | access-date = 2008-01-16 }}</ref>
* Contributes to the maintenance and function of [[pancreatic islets]]
* Stimulates the [[immune system]]
* Increases deiodination of T4 to T3<ref>T.F. Davies (ed.), A Case-Based Guide to Clinical Endocrinology, 2008, pag.16</ref>

==Clinical significance==

===Excess===

The most common disease of GH excess is a pituitary tumor composed of somatotroph cells of the anterior pituitary. These somatotroph [[adenoma]]s 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 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 [[Diabetes mellitus type 2|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 [[gigantism|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.{{Citation needed|date=June 2012}}

===Deficiency===
{{Main|Growth hormone deficiency}}
The effects of [[growth hormone deficiency|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]].<ref name=":0">{{Cite book|title=Medical-Surgical Nursing: Patient-Centered Collaborative Care|last=Ignatavicius|first=Donna|last2=Workman|first2=Linda | name-list-format = vanc |publisher=Saunders|year=2015|isbn=978-1455772551|edition=8|pages=1267}}</ref>  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]].<ref name=":0" /> However, deficiency is rare in adults, with the most common cause being a [[pituitary adenoma]].<ref name="Molitch et al. 2006">{{cite journal | vauthors = Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Shalet SM, Vance ML, Stephens PA | title = Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 91 | issue = 5 | pages = 1621–34 | date = May 2006 | pmid = 16636129 | doi = 10.1210/jc.2005-2227 }}</ref>  Other adult causes include a continuation of a childhood problem, other structural lesions or [[Injury|trauma]], and very rarely idiopathic GHD.<ref name="Molitch et al. 2006" />

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".<ref name="Molitch et al. 2006"/>

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 [[Growth hormone deficiency|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 (mood)|depression]] than those without.<ref name="Prodam_2012">{{cite journal | vauthors = Prodam F, Caputo M, Belcastro S, Garbaccio V, Zavattaro M, Samà MT, Bellone S, Pagano L, Bona G, Aimaretti G | title = Quality of life, mood disturbances and psychological parameters in adult patients with GH deficiency | journal = Panminerva Medica | volume = 54 | issue = 4 | pages = 323–31 | date = December 2012 | pmid = 23123585 | doi =  }}</ref>  While [[Growth hormone#Replacement therapy|GH replacement therapy]] has been proposed to treat depression as a result of GH deficiency, the long-term effects of such therapy are unknown.<ref name="Prodam_2012"/>

===Cognitive function===

GH has also been studied in the context of [[cognitive function]], including learning and memory.<ref name="Nyberg_2013">{{cite journal | vauthors = Nyberg F, Hallberg M | title = Growth hormone and cognitive function | journal = Nature Reviews. Endocrinology | volume = 9 | issue = 6 | pages = 357–65 | date = June 2013 | pmid = 23629538 | doi = 10.1038/nrendo.2013.78 }}</ref> 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.<ref name="Nyberg_2013"/>

==Medical uses==
{{Main|Growth hormone therapy}}

===Replacement therapy===
Treatment with exogenous GH is indicated only in limited circumstances,<ref name="Molitch et al. 2006"/> and needs regular monitoring due to the frequency and severity of side-effects. 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.

===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]], [[chronic renal failure]], [[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"). Despite the higher doses, side-effects during treatment are rare, and vary little according to the condition being treated.

One version of rHGH has also been FDA approved for maintaining muscle mass in [[wasting]] due to [[AIDS]].<ref name="pmid11367383">{{cite journal | vauthors = Gilden D | title = Human growth hormone available for AIDS wasting | journal = GMHC Treatment Issues | volume = 9 | issue = 1 | pages = 9–11 | date = January 1995 | pmid = 11367383 | doi =  }}</ref>

===Off-label use===
{{Main|HGH controversies}}

[[off-label use|Off-label]] prescription of HGH is controversial and may be illegal.<ref name="DEA: Genotropin">DEA, US Department of Justice. [http://www.deadiversion.usdoj.gov/drug_chem_info/hgh.pdf DEA: Genotropin] 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"</ref>

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.<ref name="pmid2355952">{{cite journal | vauthors = Rudman D, Feller AG, Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF, Schlenker RA, Cohn L, Rudman IW, Mattson DE | title = Effects of human growth hormone in men over 60 years old | journal = The New England Journal of Medicine | volume = 323 | issue = 1 | pages = 1–6 | date = July 1990 | pmid = 2355952 | doi = 10.1056/NEJM199007053230101 }}</ref>  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.<ref name="pmid17227934">{{cite journal | vauthors = Liu H, Bravata DM, Olkin I, Nayak S, Roberts B, Garber AM, Hoffman AR | title = Systematic review: the safety and efficacy of growth hormone in the healthy elderly | journal = Annals of Internal Medicine | volume = 146 | issue = 2 | pages = 104–15 | date = January 2007 | pmid = 17227934 | doi = 10.7326/0003-4819-146-2-200701160-00005 }}</ref><ref name="urlNo proof that growth hormone therapy makes you live longer, study finds">{{cite web | url = http://www.physorg.com/news88140162.html | title = No proof that growth hormone therapy makes you live longer, study finds  | date = 2007-01-16 | work = | publisher = PhysOrg.com | pages = | quote = | access-date = 2009-03-16}}</ref><ref>[http://www.quackwatch.com/01QuackeryRelatedTopics/hgh.html Stephen Barrett, M.D. Growth Hormone Schemes and Scams]</ref> 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".<ref name="NYTPoison">{{cite news | author = Kuczynski A  | title = Anti-Aging Potion or Poison? | publisher = New York Times | date = 1998-04-12 | url = https://www.nytimes.com/1998/04/12/style/anti-aging-potion-or-poison.html}}</ref>

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&nbsp;kg and decreased body fat by the same amount.<ref name="pmid17227934"/> 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.<ref name="pmid17227934" /> 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]].<ref>Mannfred A. Hollinger. Introduction to Pharmacology, Third Edition. CRC Press, 2002 {{ISBN|9780415280341}} [https://books.google.com/books?id=wbhAeKwhmj0C&pg=PA367 Pg 376]</ref><ref>[https://www.law.cornell.edu/uscode/text/21/333 21 U.S. Code § 333 - Penalties]</ref>

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.<ref name="DEA: Genotropin"/>  This section has also been interpreted by some doctors, most notably<ref>News Author: Laurie Barclay, MD, CME Author: Désirée Lie, MD, MSEd for Medscape. October 28, 2005 [http://www.medscape.org/viewarticle/515665 Growth Hormone Deemed Illegal for Off-Label Antiaging Use]</ref> 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.<ref name="pmid16249424">{{cite journal | vauthors = Perls TT, Reisman NR, Olshansky SJ | title = Provision or distribution of growth hormone for "antiaging": clinical and legal issues | journal = JAMA | volume = 294 | issue = 16 | pages = 2086–90 | date = October 2005 | pmid = 16249424 | doi = 10.1001/jama.294.16.2086 }}</ref>  And some articles in the popular press, such as those criticizing the pharmaceutical industry for marketing drugs for off-label use (which is clearly illegal) 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."<ref name=Caruso>David Caruso and Jeff Donn for the Associated Press.  Dec. 21, 2012 [http://bigstory.ap.org/article/ap-impact-big-pharma-cashes-hgh-abuse AP Impact: Big Pharma Cashes in on HGH Abuse]</ref><ref name=Edwards>Jim Edwards for BrandWeek.  March 20, 2006. ''[https://web.archive.org/web/20060328121242/http://www.brandweek.com/bw/news/spotlight/article_display.jsp?vnu_content_id=1002199768 Bad Medicine.]'' BrandWeek. [http://www.brandweek.com/bw/news/spotlight/article_display.jsp?vnu_content_id=1002199768 Original link broken], Created link from internet archive on August 9, 2014.  Archive date March 28, 2006.</ref>  At the same time, anti-aging clinics where doctors prescribe, administer, and sell HGH to people are big business.<ref name=Caruso/><ref name=VF>Ned Zeman for Vanity Fair.  March 2012 [http://www.vanityfair.com/hollywood/2012/03/human-grown-hormone-hollywood-201203 Hollywood's Vial Bodies]</ref>  In a 2012 article in ''[[Vanity Fair (magazine)|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."<ref name=VF/>

===Side-effects===

Injection-site reaction is common.  More rarely, patients can experience  joint swelling, joint pain, [[carpal tunnel syndrome]], and an increased risk of [[diabetes]].<ref name="pmid17227934" />   In some cases, the patient can produce an immune response against GH.  GH may also  be a risk factor for [[Hodgkin's lymphoma]].<ref name="pmid16284435">{{cite journal | vauthors = Freedman RJ, Malkovska V, LeRoith D, Collins MT | title = Hodgkin lymphoma in temporal association with growth hormone replacement | journal = Endocrine Journal | volume = 52 | issue = 5 | pages = 571–5 | date = October 2005 | pmid = 16284435 | doi = 10.1507/endocrj.52.571 }}</ref>

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.<ref name="pmid12147369">{{cite journal | vauthors = Swerdlow AJ, Higgins CD, Adlard P, Preece MA | title = Risk of cancer in patients treated with human pituitary growth hormone in the UK, 1959-85: a cohort study | journal = Lancet | volume = 360 | issue = 9329 | pages = 273–7 | date = July 2002 | pmid = 12147369 | doi = 10.1016/S0140-6736(02)09519-3 }}</ref>

==Performance enhancement==
{{Main|Growth hormone in sports}}

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.<ref name="pmid19467612">{{cite journal | vauthors = Holt RI, Erotokritou-Mulligan I, Sönksen PH | title = The history of doping and growth hormone abuse in sport | journal = Growth Hormone & IGF Research | volume = 19 | issue = 4 | pages = 320–6 | date = August 2009 | pmid = 19467612 | doi = 10.1016/j.ghir.2009.04.009 }}</ref>

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.<ref name="pmid18347346">{{cite journal | vauthors = Liu H, Bravata DM, Olkin I, Friedlander A, Liu V, Roberts B, Bendavid E, Saynina O, Salpeter SR, Garber AM, Hoffman AR | title = Systematic review: the effects of growth hormone on athletic performance | journal = Annals of Internal Medicine | volume = 148 | issue = 10 | pages = 747–58 | date = May 2008 | pmid = 18347346 | doi = 10.7326/0003-4819-148-10-200805200-00215 }}</ref><ref name="urlAthletes Don't Benefit From Human Growth Hormone, Study Finds - Bloomberg">{{cite web | url = https://www.bloomberg.com/apps/news?pid=newsarchive&sid=awlswGxIiU5c&refer=home | title = Athletes Don't Benefit From Human Growth Hormone, Study Finds  | author = Randall T | date = 2008-03-17 | format = | work = | publisher = Bloomberg | quote = | access-date = 2011-08-28 }}</ref><ref name="urlSteroid Nation: Review from Stanford says HGH no benefit as PED">{{cite web | url = http://grg51.typepad.com/steroid_nation/2008/03/review-from-sta.html | title = Steroid Nation: Review from Stanford says HGH no benefit as PED | author = Gaffney G  | date = 2008-03-17  | publisher = Steroid Nation | access-date = 2011-08-28 }}</ref>  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 supplement]]s 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.<ref name="urlAtlas Operations, Inc.">{{cite web | url = http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm215918.htm | title = Atlas Operations, Inc. | author = Singleton ER | date = 2010-06-04 | work = Warning Letter | publisher = U.S. Food and Drug Administration | access-date = 2011-08-28 }}</ref>

==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.<ref>{{cite web|url=http://www.fsis.usda.gov/fact_sheets/chicken_from_farm_to_table/index.asp#6 |title=Chicken from Farm to Table &#124; USDA Food Safety and Inspection Service |publisher=Fsis.usda.gov |date=2011-04-06 |access-date=2011-08-26 |deadurl=yes |archive-url=https://web.archive.org/web/20110903125813/http://www.fsis.usda.gov/fact_sheets/chicken_from_farm_to_table/index.asp |archive-date=2011-09-03 |df= }}</ref><ref name="USP&A FAQ">{{cite web | url=http://www.uspoultry.org/faq/faq.cfm | title=Poultry Industry Frequently Asked Questions | publisher=U.S Poultry & Egg Association | access-date=June 21, 2012}}</ref> Similarly, no chicken meat for sale in Australia is administered hormones.<ref>{{cite web | url=http://www.chicken.org.au/page.php?id=14&issue=6 | title=Hormones | publisher=Australian Chicken Meat Federation | access-date=20 June 2016}}</ref>

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.<ref name="urlwww.fda.gov">{{cite web | url = http://www.fda.gov/downloads/AnimalVeterinary/DevelopmentApprovalProcess/UCM071853.pdf | title = Center for Veterinary Medicine Master | date = 2011-04-06 | format = pdf | work = | publisher =  www.fda.gov | access-date = 2011-08-28 }}</ref><ref name="urlwww.lemars.k12.ia.us">{{cite web | url = http://www.lemars.k12.ia.us/ag/AgriScience%202%20class/Animal%20Nutrition%20Unit/Growth%20promoters%20in%20AS.pdf | title = Growth Promoters in Animal Production | year = 2006 | format = pdf | work =  | publisher =  | access-date = 2011-08-28 | deadurl = yes | archive-url = https://web.archive.org/web/20120311015321/http://www.lemars.k12.ia.us/ag/AgriScience%202%20class/Animal%20Nutrition%20Unit/Growth%20promoters%20in%20AS.pdf | archive-date = 2012-03-11 | df =  }}</ref>

==Drug development history==
{{Main|Growth hormone treatment#History}}
The identification, purification and later synthesis of growth hormone is associated with [[Choh Hao Li]].  [[Genentech]] pioneered the first use of [[recombinant DNA|recombinant]] human growth hormone for human therapy in 1981.

Prior to its production by recombinant DNA technology, growth hormone used to treat deficiencies was extracted from the [[pituitary gland]]s of [[cadaver]]s.  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.<ref name = "Maybe_1984">{{cite book | author = Maybe, Nancy G | editor = Arthur P. Bollon | title = Recombinant DNA products: insulin, interferon, and growth hormone | edition = | publisher = CRC Press | location = Boca Raton | year = 1984 | origyear = | pages = | chapter = Direct expression of human growth in ''Escherichia coli'' with the lipoprotein promoter | quote = | isbn = 0-8493-5542-7 }}</ref>  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.<ref name="pmid13421688">{{cite journal | vauthors = Beck JC, Mcgarry EE, Dyrenfurth I, Venning EH | title = Metabolic effects of human and monkey growth hormone in man | journal = Science | volume = 125 | issue = 3253 | pages = 884–5 | date = May 1957 | pmid = 13421688 | doi = 10.1126/science.125.3253.884 }}</ref> 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&nbsp;... (and) there was a retention of potassium, phosphorus, calcium, and sodium.&nbsp;... There was a gain in body weight during both periods.&nbsp;... 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.&nbsp;... 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."<ref name="pmid13421688"/>  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.<ref name="pmid13595475">{{cite journal | vauthors = Beck JC, McGARRY EE, Dyrenfurth I, Venning EH | title = The metabolic effects of human and monkey growth hormone in man | journal = Annals of Internal Medicine | volume = 49 | issue = 5 | pages = 1090–105 | date = November 1958 | pmid = 13595475 | doi = 10.7326/0003-4819-49-5-1090 }}</ref>

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.<ref name = "isbn0-07-144011-9"/>

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 ([[Eli Lilly and Company|Lilly]]), Genotropin ([[Pfizer]]), Norditropin ([[Novo Nordisk|Novo]]),  and Saizen ([[Merck Serono]]). In 2006, the U.S. Food and Drug Administration (FDA) approved a version of [[rHGH]] called [[Omnitrope]] (Sandoz).<ref name="FDA_biosimilars">{{citation |url=http://www.fda.gov/ohrms/dockets/dockets/04P0231/04P-0231-pdn0001.pdf |title=FDA Response to three Citizen Petitions against biosimilars |work=FDA |date=30 May 2006 |access-date=23 November 2015}}</ref>  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<ref name="urlGenentech and Alkermes Announce Decision to Discontinue Commercialization of Nutropin Depot">{{cite web | url = http://findarticles.com/p/articles/mi_m0EIN/is_2004_June_1/ai_n6050768 | title = Genentech and Alkermes Announce Decision to Discontinue Commercialization of Nutropin Depot | date = 2004-06-01 | work = Press Release | publisher =  Business Wire | access-date = 2011-08-28 }}</ref>).

==See also==
* [[Somatopause]]

== References ==
{{Reflist|2}}

== External links ==
*{{Commonscat-inline|Growth hormones}}

{{Hormones}}
{{GH/IGF-1 axis signaling modulators}}
{{Authority control}}

{{DEFAULTSORT:Growth Hormone}}
[[Category:Growth hormones| ]]
[[Category:Pfizer]]
[[Category:Anterior pituitary hormones]]
[[Category:Hormones of the somatotropic axis]]
[[Category:Recombinant proteins]]
[[Category:Peptide hormones]]
[[Category:Anti-aging substances]]
[[Category:World Anti-Doping Agency prohibited substances]]