Editing Growth hormone (section)

===Regulation===
{{See also|Hypothalamic–pituitary–somatotropic axis}}
[[File:1809 Hormonal Regulation of Growth.jpg|thumb|500px|right|Flowchart showing hormonal regulation of growth]]
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 | publisher = Pearson Education Inc | location = Upper Saddle River, NJ | year = 2009 | pages = 616–617 | isbn = 978-0-321-53910-6 }}</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>
Maximal secretion of GH may occur within minutes of the onset of  [[slow-wave sleep|slow-wave]] (SW) sleep (stage III or IV).<ref name="pmid10984255">{{cite journal | vauthors = Van Cauter E, Copinschi G | title = Interrelationships between growth hormone and sleep | journal = Growth Hormone & IGF Research | volume = 10 | issue = Suppl B | pages = S57–62 | date = April 2000 | pmid = 10984255 | doi = 10.1016/s1096-6374(00)80011-8 }}</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 | s2cid = 23663131 }}</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 | doi-access = free }}</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 | s2cid = 16101442 }}</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 | doi-broken-date = 1 November 2024 }}</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 | year = 2007 | publisher= McGraw-Hill Medical | location = New York | isbn = 978-0-07-144011-0 | pages = 193–201 }}</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 | s2cid = 3328167 }}</ref>

Stimulators{{how much|date=January 2021}} 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 | s2cid = 6263928 }}</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 | doi-access = free }}</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 | s2cid = 20688016 | doi-access = free }}</ref>
** Increased [[androgen]] secretion during puberty (in males from testes and in females from adrenal cortex)
** [[Testosterone]] and [[DHEA]]
** [[Estrogen]]
* [[Clonidine]], [[moxonidine]] 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 | pages = 37–40 | year = 1991 | issue = Suppl 1 | 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]] or [[moxonidine]].<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 | doi-access = free }}</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 | s2cid = 37559511 }}</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 | s2cid = 7488757 }}</ref> [[pramipexole]],<ref>{{Cite journal |last1=Samuels |first1=Ebony R |last2=Hou |first2=Ruihua H |last3=Langley |first3=Robert W |last4=Szabadi |first4=Elemer |last5=Bradshaw |first5=Christopher M |date=June 19, 2007 |title=Comparison of pramipexole with and without domperidone co-administration on alertness, autonomic, and endocrine functions in healthy volunteers |journal=British Journal of Clinical Pharmacology |volume=64 |issue=5 |pages=591–602 |doi=10.1111/j.1365-2125.2007.02938.x |issn=0306-5251 |pmc=2203276 |pmid=17578485}}</ref> [[Ornithine|ornitine]], [[lysine]], [[tryptophan]], [[γ-Aminobutyric acid]] 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 | pages = S10–7 | date = June 2004 | pmid = 15135771 | doi = 10.1016/j.ghir.2004.03.006 }}</ref>
* [[Glucagon]]
* [[Sodium oxybate]] or [[Gamma-Hydroxybutyric acid|γ-Hydroxybutyric acid]]
* [[Niacin (substance)|Niacin]] as nicotinic acid (vitamin B<sub>3</sub>)<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>
* [[Insulin]]<ref>"Greenspan's Basic & Clinical Endocrinology 10th Edition"</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 }}</ref>

''Inhibitors''{{how much|date=January 2021}} 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 | 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]]
* [[Phenothiazine]]s

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 | s2cid = 40503492 }}</ref>