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==Overview==
{{Distinguish|Somatocrinin|Somatomedin}}
{{Protein
{{Infobox gene}}
|Name=Somatostatin
 
|image=somatostatin.png
'''Somatostatin''', also known as '''growth hormone–inhibiting hormone''' ('''GHIH''') or by [[#Nomenclature|several other names]], is a [[peptide hormone]] that regulates the [[endocrine system]] and affects [[neurotransmission]] and [[cell proliferation]] via interaction with [[G protein-coupled]] [[somatostatin receptors]] and inhibition of the release of numerous secondary hormones. Somatostatin inhibits insulin and glucagon secretion.<ref>"somatostatin". Encyclopædia Britannica. Encyclopædia Britannica Online. Encyclopædia Britannica Inc., 2016. Web. 04 mag. 2016 <http://www.britannica.com/science/somatostatin>.</ref>
|caption=
 
|Symbol=SST
Somatostatin has two active forms produced by alternative cleavage of a single preproprotein: one of 14 [[amino acid]]s (shown in infobox to right), the other of 28 amino acids.<ref name="GP5416">{{cite web|url=http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch4/s5ch4_16.htm |title=Sect. 5, Ch. 4: Structure, Synthesis, and Secretion of Somatostatin |accessdate=2008-02-19 |author=Costoff A |date= |work=Endocrinology: The Endocrine Pancreas |publisher=Medical College of Georgia |pages=16 |language= |quote= |deadurl=yes |archiveurl=https://web.archive.org/web/20080405060426/http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch4/s5ch4_16.htm |archivedate=April 5, 2008 }}</ref> <ref>[https://www.ncbi.nlm.nih.gov/protein/NP_001039 somatostatin preproprotein &#91;Homo sapiens&#93; See Features]</ref>
|AltSymbols=
|HGNCid=11329
|Chromosome=3
|Arm=q
|Band=28
|LocusSupplementaryData=
|ECnumber=
|OMIM=182450
|EntrezGene=6750
|RefSeq=NM_001048
|UniProt=P61278
|PDB=
}}
{{SI}}
{{GS}}


{{Editor Join}}
Among the [[vertebrates]], there exist six different somatostatin genes that have been named SS1, SS2, SS3, SS4, SS5, and SS6.<ref name="Liu">{{cite journal |vauthors=Liu Y, Lu D, Zhang Y, Li S, Liu X, Lin H | year = 2010 | title = The evolution of somatostatin in vertebrates | url = | journal = Gene | volume = 463 | issue = 1–2| pages = 21–28 |doi=10.1016/j.gene.2010.04.016 | pmid=20472043}}</ref> [[Zebrafish]] have all 6.<ref name="Liu"/> The six different genes along with the five different [[somatostatin receptors]] allows somatostatin to possess a large range of functions.<ref name="Gahete">{{cite journal |vauthors=Gahete MD, Cordoba-Chacón J, Duran-Prado M, Malagón MM, Martinez-Fuentes AJ, Gracia-Navarro F, Luque RM, Castaño JP | year = 2010 | title = Somatostatin and its receptors from fish to mammals | url = | journal = Annals of the New York Academy of Sciences | volume = 1200 | issue = | pages = 43–52 | doi = 10.1111/j.1749-6632.2010.05511.x | pmid = 20633132 }}</ref>
__NOTOC__
Humans have only one somatostatin gene, SST.<ref name="entrez">{{cite web | title = Entrez Gene: Somatostatin | url = https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=retrieve&list_uids=6750 }}</ref><ref name="pmid6126875">{{cite journal |vauthors=Shen LP, Pictet RL, Rutter WJ | title = Human somatostatin I: sequence of the cDNA | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 79 | issue = 15 | pages = 4575–9 |date=August 1982 | pmid = 6126875 | pmc = 346717 | doi = 10.1073/pnas.79.15.4575}}</ref><ref name="pmid6142531">{{cite journal |vauthors=Shen LP, Rutter WJ | title = Sequence of the human somatostatin I gene | journal = Science | volume = 224 | issue = 4645 | pages = 168–71 |date=April 1984 | pmid = 6142531 | doi = 10.1126/science.6142531}}</ref>
'''Somatostatin''' (also known as '''growth hormone inhibiting hormone''' ('''GHIH''') or '''somatotropin release-inhibiting hormone''' ('''SRIF''')) is a [[peptide hormone]] that regulates the [[endocrine system]] and affects [[neurotransmission]] and [[cell proliferation]] via interaction with [[G-protein-coupled]] [[somatostatin receptors]] and inhibition of the release of numerous secondary hormones.  


Somatostatin has two active forms produced by alternative cleavage of a single preproprotein: one of 14 [[amino acid]]s, the other of 28 amino acids.<ref name="GP5416">{{GeorgiaPhysiology|5/5ch4/s5ch4_16}}</ref>
==Nomenclature==
Synonyms of ''somatostatin'' are as follows:  
* growth hormone–inhibiting hormone (GHIH)
* growth hormone release–inhibiting hormone (GHRIH)
* somatotropin release–inhibiting factor (SRIF)
* somatotropin release–inhibiting hormone (SRIH)


==Production==
==Production==
===Digestive system===
===Digestive system===


Somatostatin is secreted in several locations in the digestive system:
Somatostatin is secreted at several locations in the digestive system:
* [[stomach]]
* [[Delta cells]] in the [[pyloric antrum]], the [[duodenum]] and the [[pancreatic islets]]<ref name="isbn9781437717532">{{cite book |author1=Boron, Walter F.  |author2=Boulpaep, Emile L. | title = Medical Physiology, 2e Updated Edition, 2nd Edition | publisher = Elsevier | location = Philadelphia, PA | year = 2012 | edition = 2nd | isbn = 9781437717532 | oclc = | doi = }}</ref>
* [[intestine]]
 
* [[delta cells]] of the [[pancreas]]<ref>Costanzo, LS. ''Board Review Series: Physiology'' 3rd Ed. Lippincott, Williams & Wilkins. 2003. p. 280.</ref>
Somatostatin released in the [[pyloric antrum]] travels via the portal venous system to the heart, then enters the systemic circulation to reach the locations where it will exert its inhibitory effects. In addition, somatostatin release from delta cells can act in a [[paracrine]] manner.<ref name="isbn9781437717532"/>
 
In the stomach, somatostatin acts directly on the acid-producing [[parietal cells]] via a G-protein coupled receptor (which inhibits adenylate cyclase, thus effectively antagonising the stimulatory effect of histamine) to reduce acid secretion.<ref name="isbn9781437717532"/> Somatostatin can also indirectly decrease stomach acid production by preventing the release of other hormones, including [[gastrin]], [[secretin]] and [[histamine]] which effectively slows down the digestive process.


===Brain===
===Brain===
Somatostatin is produced by [[neuroendocrine]] neurons of the [[periventricular nucleus]] of the [[hypothalamus]]. These neurons project to the [[median eminence]], where somatostatin is released from neurosecretory nerve endings into the hypothalamo-hypophysial portal circulation. These blood vessels carry somatostatin to the [[anterior pituitary gland]], where somatostatin inhibits the secretion of growth hormone from [[somatotrope]] cells. The somatostatin neurons in the periventricular nucleus mediate negative feedback effects of growth hormone on its own release; the somatostatin neurons respond to high circulating concentrations of growth hormone and [[somatomedin]]s by increasing the release of somatostatin, so reducing the rate of secretion of growth hormone.
{|Somatostatin is also produced in the hypothalamus, it will inhibit GH and TSH.
| [[File:Sst, ISH, E15.5, telencephalon.jpg|thumbnail|left| [http://developingmouse.brain-map.org/data/Sst/100053205.html?ispopup=true Sst] is expressed in interneurons in the telencephalon of the embryonic day 15.5 mouse. [[Allen Brain Atlas]]es]]
| [[File:Sst, ISH, p56 mouse.jpg|thumbnail|left| [http://mouse.brain-map.org/experiment/show/1001 Sst] expression in the adult mouse.  [[Allen Brain Atlas]]es]]
|}
Somatostatin is produced by [[neuroendocrine]] neurons of the [[ventromedial nucleus]] of the [[hypothalamus]]. These neurons project to the [[median eminence]], where somatostatin is released from neurosecretory nerve endings into the [[Hypophyseal portal system|hypothalamo-hypophysial system]] through neuron axons. Somatostatin is then carried to the [[anterior pituitary gland]], where it inhibits the secretion of [[growth hormone]] from [[somatotrope]] cells. The somatostatin neurons in the periventricular nucleus mediate negative feedback effects of [[growth hormone]] on its own release; the somatostatin neurons respond to high circulating concentrations of [[growth hormone]] and [[somatomedin]]s by increasing the release of somatostatin, so reducing the rate of secretion of [[growth hormone]].


Somatostatin is also produced by several other populations that project centrally - i.e. to other areas of the brain, and somatostatin receptors are expressed at many different sites in the brain. In particular, there are populations of somatostatin neurons in the [[arcuate nucleus]], the [[hippocampus]] and the brainstem [[nucleus of the solitary tract]].
Somatostatin is also produced by several other populations that project centrally, i.e., to other areas of the brain, and somatostatin receptors are expressed at many different sites in the brain. In particular, there are populations of somatostatin neurons in the [[arcuate nucleus]],{{Citation needed|date=August 2011}} the [[hippocampus]],{{Citation needed|date=August 2011}} and the brainstem [[nucleus of the solitary tract]].{{Citation needed|date=August 2011}}


==Actions==
==Actions==
[[Image:Control-of-stomach-acid-sec.png|thumb|left|250px|[[D cell (biology)|D cell]] is visible at upper right, and somatostatinis represented by middle arrow pointing left]]
[[Image:Control-of-stomach-acid-sec.png|thumb|350px|[[D cell (biology)|D cell]] is visible at upper-right, and somatostatin is represented by middle arrow pointing left]]


Somatostatin is classified as an [[inhibitory]] hormone,<ref name="GP5416"> </ref> whose actions are spread to different parts of the body:
Somatostatin is classified as an [[inhibitory]] hormone,<ref name="GP5416" /> and is induced by low pH.{{Citation needed|date=May 2014}}. Its actions are spread to different parts of the body.


===Anterior pituitary===
===Anterior pituitary===
In the [[anterior pituitary gland]], the effects of somatostatin are:
In the [[anterior pituitary gland]], the effects of somatostatin are:
* Inhibit the release of [[growth hormone]] (GH) <ref name="Colorado"> http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/otherendo/somatostatin.html Colorado State University - Biomedical Hypertextbooks - Somatostatin </ref> (thus opposing the effects of [[Growth Hormone-Releasing Hormone]] (GHRH))
* Inhibit the release of [[growth hormone]] (GH)<ref name="titleSomatostatin">{{cite web | url = http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/otherendo/somatostatin.html | title = Somatostatin | accessdate = 2008-02-19 | author = Bowen R | date = 2002-12-14 | work = Biomedical Hypertextbooks | publisher = Colorado State University | pages = | language = | archiveurl = | archivedate = | quote = }}</ref> (thus opposing the effects of [[growth hormone–releasing hormone]] (GHRH))
* Inhibit the release of [[thyroid-stimulating hormone]] (TSH)
* Inhibit the release of [[thyroid-stimulating hormone]] (TSH)<ref>First Aid for the USMLE Step 1, 2010. Page 286.</ref>
* Inhibit adenylyl cyclase in parietal cells.
* Inhibits the release of prolactin (PRL)


===Gastrointestinal system===
===Gastrointestinal system===
* Suppress the release of [[gastrointestinal hormone]]s
 
* Somatostatin is homologous with [[CORT|cortistatin]] (see [[somatostatin family]]) and suppresses the release of [[gastrointestinal hormone]]s
** [[Gastrin]]
** [[Gastrin]]
** [[Cholecystokinin]] (CCK)
** [[Cholecystokinin]] (CCK)
Line 59: Line 58:
** [[Gastric inhibitory polypeptide]] (GIP)
** [[Gastric inhibitory polypeptide]] (GIP)
** [[Enteroglucagon]]
** [[Enteroglucagon]]
* Lowers the rate of gastric emptying, and reduces smooth muscle contractions and blood flow within the intestine<ref name="Colorado"> </ref>
* Decrease rate of gastric emptying, and reduces smooth muscle contractions and blood flow within the intestine<ref name="titleSomatostatin"/>
* Suppress the release of pancreatic hormones
* Suppresses the release of pancreatic hormones
** Inhibit the release of [[insulin]]<ref name="GP5417">{{GeorgiaPhysiology|5/5ch4/s5ch4_17}}</ref>
** Somatostatin release is triggered by the beta cell peptide Urocortin3 (Ucn3) to inhibit [[insulin]] release.<ref name="GP5417">{{cite web|url=http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch4/s5ch4_17.htm |title=Sect. 5, Ch. 4: Structure, Synthesis, and Secretion of Somatostatin |accessdate=2008-02-19 |author=Costoff A |date= |work=Endocrinology: The Endocrine Pancreas |publisher=Medical College of Georgia |pages=17 |language= |archiveurl=https://web.archive.org/web/20080331235236/http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch4/s5ch4_17.htm |archivedate=March 31, 2008 |quote= |deadurl=yes }}</ref><ref>{{Cite journal|vauthors=Van der Meulen T, Donaldson CJ, Cáceres E, Hunter AE, Cowing-Zitron C, Pound LD, Adams MW, Zembrzycki A, Grove KL, Huising MO |date=2016-06-15|title=Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion|url=http://www.nature.com/nm/journal/v21/n7/full/nm.3872.html|journal=Nature Medicine|doi=10.1038/nm.3872|pmid=26076035|access-date=2016-05-30|volume=21|pages=769–76|pmc=4496282}}</ref>
** Inhibit the release of [[glucagon]]<ref name="GP5417"> </ref>
** Inhibits the release of [[glucagon]]<ref name="GP5417"/>
* Suppress the exocrine secretory action of [[pancreas]].
* Suppresses the exocrine secretory action of [[pancreas]].


==Synthetic substitutes==
==Synthetic substitutes==
'''[[Octreotide]]''' (brand name ''Sandostatin'', [[Novartis|Novartis Pharmaceuticals]]) is an [[peptide|octopeptide]] that mimics natural somatostatin pharmacologically, though is a more potent inhibitor of [[growth hormone]], [[glucagon]], and [[insulin]] than the natural hormone.  
{{Refimprove section|date=March 2009}}
[[Octreotide]] (brand name ''Sandostatin'', [[Novartis|Novartis Pharmaceuticals]]) is an [[peptide|octapeptide]] that mimics natural somatostatin pharmacologically, though is a more potent inhibitor of [[growth hormone]], glucagon, and [[insulin]] than the natural hormone and has a much longer [[half-life]] (approximately 90 minutes, compared to 2–3 minutes for somatostatin). Since it is absorbed poorly from the gut, it is administered parenterally (subcutaneously, intramuscularly, or intravenously). It is indicated for [[symptomatic treatment]] of  [[carcinoid syndrome]] and [[acromegaly]]. It is also finding increased use in polycystic diseases of the liver and kidney.
 
[[Lanreotide]] (brand name ''Somatuline'', [[Ipsen|Ipsen Pharmaceuticals]])is a medication used in the management of acromegaly and symptoms caused by neuroendocrine tumors, most notably carcinoid syndrome. It is a long-acting [[structural analog|analog]] of somatostatin, like octreotide. It is available in several countries, including the United Kingdom, Australia, and Canada, and was approved for sale in the United States by the Food and Drug Administration (FDA) on August 30, 2007.
 
==Evolutionary history==
There are six somatostatin genes that have been discovered in [[vertebrates]]. The current proposed history as to how these six genes arose is based on the three whole-genome duplication events that took place in vertebrate evolution along with local duplications in [[teleost]] fish. An ancestral somatostatin gene was duplicated during the first [[whole-genome duplication event]] (1R) to create SS1 and SS2. These two genes were duplicated during the second whole-genome duplication event (2R) to create four new somatostatin genes: SS1, SS2, SS3, and one gene that was lost during the evolution of vertebrates. [[Tetrapods]] retained SS1 (also known as SS-14 and SS-28) and SS2 (also known as [[Cortistatin (neuropeptide)|cortistatin]]) after the split in the [[sarcopterygii]] and [[actinopterygii]] lineage split. In [[teleost]] fish, SS1, SS2, and SS3 were duplicated during the third whole-genome duplication event (3R) to create SS1, SS2, SS4, SS5, and two genes that were lost during the evolution of teleost fish. SS1 and SS2 went through local duplications to give rise to SS6 and SS3.<ref name="Liu"/>
 
==See also==
* [[Hypothalamic–pituitary–somatic axis]]


==References==
==References==
<references/>
{{Reflist}}
 
==Further reading==
{{refbegin | 2}}
{{PBB_Further reading
| citations =
*{{cite journal  |vauthors=Florio T, Schettini G |title=[Somatostatin and its receptors. Role in the control of cell proliferation] |journal=Minerva Endocrinol. |volume=26 |issue= 3 |pages= 91–102 |year= 2002 |pmid= 11753230 |doi=  }}
*{{cite journal  |vauthors=Yamada Y, Reisine T, Law SF, etal |title=Somatostatin receptors, an expanding gene family: cloning and functional characterization of human SSTR3, a protein coupled to adenylyl cyclase |journal=Mol. Endocrinol. |volume=6 |issue= 12 |pages= 2136–42 |year= 1993 |pmid= 1337145 |doi=10.1210/me.6.12.2136  }}
*{{cite journal  |vauthors=Yamada Y, Post SR, Wang K, etal |title=Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue= 1 |pages= 251–5 |year= 1992 |pmid= 1346068| doi=10.1073/pnas.89.1.251  | pmc=48214}}
*{{cite journal  |vauthors=Brazeau P, Vale W, Burgus R, etal |title=Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone |journal=Science |volume=179 |issue= 4068 |pages= 77–9 |year= 1973 |pmid= 4682131| doi=10.1126/science.179.4068.77}}
*{{cite journal  |vauthors=Shen LP, Pictet RL, Rutter WJ |title=Human somatostatin I: sequence of the cDNA |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=79 |issue= 15 |pages= 4575–9 |year= 1982 |pmid= 6126875| doi=10.1073/pnas.79.15.4575  | pmc=346717}}
*{{cite journal  |vauthors=Shen LP, Rutter WJ |title=Sequence of the human somatostatin I gene |journal=Science |volume=224 |issue= 4645 |pages= 168–71 |year= 1984 |pmid= 6142531| doi=10.1126/science.6142531}}
*{{cite journal  |vauthors=Montminy MR, Goodman RH, Horovitch SJ, Habener JF |title=Primary structure of the gene encoding rat preprosomatostatin |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=81 |issue= 11 |pages= 3337–40 |year= 1984 |pmid= 6145156| doi=10.1073/pnas.81.11.3337  | pmc=345502}}
*{{cite journal  |vauthors=Zabel BU, Naylor SL, Sakaguchi AY, etal |title=High-resolution chromosomal localization of human genes for amylase, proopiomelanocortin, somatostatin, and a DNA fragment (D3S1) by in situ hybridization |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=80 |issue= 22 |pages= 6932–6 |year= 1984 |pmid= 6196780 |doi=10.1073/pnas.80.22.6932  | pmc=390100  }}
*{{cite journal  |vauthors=Panetta R, Greenwood MT, Warszynska A, etal |title=Molecular cloning, functional characterization, and chromosomal localization of a human somatostatin receptor (somatostatin receptor type 5) with preferential affinity for somatostatin-28 |journal=Mol. Pharmacol. |volume=45 |issue= 3 |pages= 417–27 |year= 1994 |pmid= 7908405 |doi=  }}
*{{cite journal  |vauthors=Demchyshyn LL, Srikant CB, Sunahara RK, etal |title=Cloning and expression of a human somatostatin-14-selective receptor variant (somatostatin receptor 4) located on chromosome 20 |journal=Mol. Pharmacol. |volume=43 |issue= 6 |pages= 894–901 |year= 1993 |pmid= 8100352 |doi=  }}
*{{cite journal  |vauthors=Kaupmann K, Bruns C, Hoyer D, etal |title=Distribution and second messenger coupling of four somatostatin receptor subtypes expressed in brain |journal=FEBS Lett. |volume=331 |issue= 1–2 |pages= 53–9 |year= 1993 |pmid= 8405411| doi=10.1016/0014-5793(93)80296-7}}
*{{cite journal  |vauthors=Aguila MC, Rodriguez AM, Aguila-Mansilla HN, Lee WT |title=Somatostatin antisense oligodeoxynucleotide-mediated stimulation of lymphocyte proliferation in culture |journal=Endocrinology |volume=137 |issue= 5 |pages= 1585–90 |year= 1996 |pmid= 8612489| doi=10.1210/en.137.5.1585}}
*{{cite journal  |vauthors=Sharma K, Patel YC, Srikant CB |title=Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3 |journal=Mol. Endocrinol. |volume=10 |issue= 12 |pages= 1688–96 |year= 1997 |pmid= 8961277 |doi=10.1210/me.10.12.1688  }}
*{{cite journal  |vauthors=Dournaud P, Boudin H, Schonbrunn A, etal |title=Interrelationships between somatostatin sst2A receptors and somatostatin-containing axons in rat brain: evidence for regulation of cell surface receptors by endogenous somatostatin |journal=J. Neurosci. |volume=18 |issue= 3 |pages= 1056–71 |year= 1998 |pmid= 9437026 |doi=  }}
*{{cite journal  |vauthors=Barnea A, Roberts J, Ho RH |title=Evidence for a synergistic effect of the HIV-1 envelope protein gp120 and brain-derived neurotrophic factor (BDNF) leading to enhanced expression of somatostatin neurons in aggregate cultures derived from the human fetal cortex |journal=Brain Res. |volume=815 |issue= 2 |pages= 349–57 |year= 1999 |pmid= 9878821| doi=10.1016/S0006-8993(98)01098-1}}
*{{cite journal  |vauthors=Ferone D, van Hagen PM, van Koetsveld PM, etal |title=In vitro characterization of somatostatin receptors in the human thymus and effects of somatostatin and octreotide on cultured thymic epithelial cells |journal=Endocrinology |volume=140 |issue= 1 |pages= 373–80 |year= 1999 |pmid= 9886848 |doi=10.1210/en.140.1.373  }}
*{{cite journal  |vauthors=Brakch N, Lazar N, Panchal M, etal |title=The somatostatin-28(1-12)-NPAMAP sequence: an essential helical-promoting motif governing prosomatostatin processing at mono- and dibasic sites |journal=Biochemistry |volume=41 |issue= 5 |pages= 1630–9 |year= 2002 |pmid= 11814357| doi=10.1021/bi011928m}}
*{{cite journal  |vauthors=Oomen SP, van Hennik PB, Antonissen C, etal |title=Somatostatin is a selective chemoattractant for primitive (CD34(+)) hematopoietic progenitor cells |journal=Exp. Hematol. |volume=30 |issue= 2 |pages= 116–25 |year= 2002 |pmid= 11823046| doi=10.1016/S0301-472X(01)00772-X}}
*{{cite journal  |vauthors=Simonetti M, Di BC |title=Structural motifs in the maturation process of peptide hormones. The somatostatin precursor. I. A CD conformational study |journal=J. Pept. Sci. |volume=8 |issue= 2 |pages= 66–79 |year= 2002 |pmid= 11860030 |doi= 10.1002/psc.370 }}
}}
{{refend}}


{{Hormones}}
{{Hormones}}
{{Gastrointestinal physiology}}
{{Gastrointestinal physiology}}
{{Neuropeptides}}
{{Neuropeptides}}
{{Pituitary and hypothalamic hormones and analogues}}
{{GH/IGF-1 axis signaling modulators}}
 
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[[Category:Antidiarrhoeals]]
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[[Category:Hormonal agents]]
[[Category:Endocrine system]]
[[Category:Endocrine system]]
[[Category:Pancreatic hormones]]
[[Category:Hormones of the somatotropic axis]]
[[Category:Hormones of the hypothalamus]]
[[Category:Somatotropic axis]]
[[Category:Neuropeptides]]
[[Category:Neuropeptides]]
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[[Category:Neuroendocrinology]]
[[Category:Endocrinology]]
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[[Category:Somatostatin receptor agonists]]
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[[bg:Соматостатин]]
[[cs:Somatostatin]]
[[da:Somatostatin]]
[[de:Somatostatin]]
[[dv:ސޯމަޓަސްޓެޓިން]]
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[[fr:Somatostatine]]
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[[he:סומטוסטטין]]
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[[ja:ソマトスタチン]]
[[no:Somatostatin]]
[[pl:Somatostatyna]]
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Somatostatin, also known as growth hormone–inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones. Somatostatin inhibits insulin and glucagon secretion.[1]

Somatostatin has two active forms produced by alternative cleavage of a single preproprotein: one of 14 amino acids (shown in infobox to right), the other of 28 amino acids.[2] [3]

Among the vertebrates, there exist six different somatostatin genes that have been named SS1, SS2, SS3, SS4, SS5, and SS6.[4] Zebrafish have all 6.[4] The six different genes along with the five different somatostatin receptors allows somatostatin to possess a large range of functions.[5] Humans have only one somatostatin gene, SST.[6][7][8]

Nomenclature

Synonyms of somatostatin are as follows:

  • growth hormone–inhibiting hormone (GHIH)
  • growth hormone release–inhibiting hormone (GHRIH)
  • somatotropin release–inhibiting factor (SRIF)
  • somatotropin release–inhibiting hormone (SRIH)

Production

Digestive system

Somatostatin is secreted at several locations in the digestive system:

Somatostatin released in the pyloric antrum travels via the portal venous system to the heart, then enters the systemic circulation to reach the locations where it will exert its inhibitory effects. In addition, somatostatin release from delta cells can act in a paracrine manner.[9]

In the stomach, somatostatin acts directly on the acid-producing parietal cells via a G-protein coupled receptor (which inhibits adenylate cyclase, thus effectively antagonising the stimulatory effect of histamine) to reduce acid secretion.[9] Somatostatin can also indirectly decrease stomach acid production by preventing the release of other hormones, including gastrin, secretin and histamine which effectively slows down the digestive process.

Brain

File:Sst, ISH, E15.5, telencephalon.jpg
Sst is expressed in interneurons in the telencephalon of the embryonic day 15.5 mouse. Allen Brain Atlases
File:Sst, ISH, p56 mouse.jpg
Sst expression in the adult mouse. Allen Brain Atlases

Somatostatin is produced by neuroendocrine neurons of the ventromedial nucleus of the hypothalamus. These neurons project to the median eminence, where somatostatin is released from neurosecretory nerve endings into the hypothalamo-hypophysial system through neuron axons. Somatostatin is then carried to the anterior pituitary gland, where it inhibits the secretion of growth hormone from somatotrope cells. The somatostatin neurons in the periventricular nucleus mediate negative feedback effects of growth hormone on its own release; the somatostatin neurons respond to high circulating concentrations of growth hormone and somatomedins by increasing the release of somatostatin, so reducing the rate of secretion of growth hormone.

Somatostatin is also produced by several other populations that project centrally, i.e., to other areas of the brain, and somatostatin receptors are expressed at many different sites in the brain. In particular, there are populations of somatostatin neurons in the arcuate nucleus,[citation needed] the hippocampus,[citation needed] and the brainstem nucleus of the solitary tract.[citation needed]

Actions

D cell is visible at upper-right, and somatostatin is represented by middle arrow pointing left

Somatostatin is classified as an inhibitory hormone,[2] and is induced by low pH.[citation needed]. Its actions are spread to different parts of the body.

Anterior pituitary

In the anterior pituitary gland, the effects of somatostatin are:

Gastrointestinal system

Synthetic substitutes

Octreotide (brand name Sandostatin, Novartis Pharmaceuticals) is an octapeptide that mimics natural somatostatin pharmacologically, though is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone and has a much longer half-life (approximately 90 minutes, compared to 2–3 minutes for somatostatin). Since it is absorbed poorly from the gut, it is administered parenterally (subcutaneously, intramuscularly, or intravenously). It is indicated for symptomatic treatment of carcinoid syndrome and acromegaly. It is also finding increased use in polycystic diseases of the liver and kidney.

Lanreotide (brand name Somatuline, Ipsen Pharmaceuticals)is a medication used in the management of acromegaly and symptoms caused by neuroendocrine tumors, most notably carcinoid syndrome. It is a long-acting analog of somatostatin, like octreotide. It is available in several countries, including the United Kingdom, Australia, and Canada, and was approved for sale in the United States by the Food and Drug Administration (FDA) on August 30, 2007.

Evolutionary history

There are six somatostatin genes that have been discovered in vertebrates. The current proposed history as to how these six genes arose is based on the three whole-genome duplication events that took place in vertebrate evolution along with local duplications in teleost fish. An ancestral somatostatin gene was duplicated during the first whole-genome duplication event (1R) to create SS1 and SS2. These two genes were duplicated during the second whole-genome duplication event (2R) to create four new somatostatin genes: SS1, SS2, SS3, and one gene that was lost during the evolution of vertebrates. Tetrapods retained SS1 (also known as SS-14 and SS-28) and SS2 (also known as cortistatin) after the split in the sarcopterygii and actinopterygii lineage split. In teleost fish, SS1, SS2, and SS3 were duplicated during the third whole-genome duplication event (3R) to create SS1, SS2, SS4, SS5, and two genes that were lost during the evolution of teleost fish. SS1 and SS2 went through local duplications to give rise to SS6 and SS3.[4]

See also

References

  1. "somatostatin". Encyclopædia Britannica. Encyclopædia Britannica Online. Encyclopædia Britannica Inc., 2016. Web. 04 mag. 2016 <http://www.britannica.com/science/somatostatin>.
  2. 2.0 2.1 Costoff A. "Sect. 5, Ch. 4: Structure, Synthesis, and Secretion of Somatostatin". Endocrinology: The Endocrine Pancreas. Medical College of Georgia. p. 16. Archived from the original on April 5, 2008. Retrieved 2008-02-19.
  3. somatostatin preproprotein [Homo sapiens] See Features
  4. 4.0 4.1 4.2 Liu Y, Lu D, Zhang Y, Li S, Liu X, Lin H (2010). "The evolution of somatostatin in vertebrates". Gene. 463 (1–2): 21–28. doi:10.1016/j.gene.2010.04.016. PMID 20472043.
  5. Gahete MD, Cordoba-Chacón J, Duran-Prado M, Malagón MM, Martinez-Fuentes AJ, Gracia-Navarro F, Luque RM, Castaño JP (2010). "Somatostatin and its receptors from fish to mammals". Annals of the New York Academy of Sciences. 1200: 43–52. doi:10.1111/j.1749-6632.2010.05511.x. PMID 20633132.
  6. "Entrez Gene: Somatostatin".
  7. Shen LP, Pictet RL, Rutter WJ (August 1982). "Human somatostatin I: sequence of the cDNA". Proc. Natl. Acad. Sci. U.S.A. 79 (15): 4575–9. doi:10.1073/pnas.79.15.4575. PMC 346717. PMID 6126875.
  8. Shen LP, Rutter WJ (April 1984). "Sequence of the human somatostatin I gene". Science. 224 (4645): 168–71. doi:10.1126/science.6142531. PMID 6142531.
  9. 9.0 9.1 9.2 Boron, Walter F.; Boulpaep, Emile L. (2012). Medical Physiology, 2e Updated Edition, 2nd Edition (2nd ed.). Philadelphia, PA: Elsevier. ISBN 9781437717532.
  10. 10.0 10.1 Bowen R (2002-12-14). "Somatostatin". Biomedical Hypertextbooks. Colorado State University. Retrieved 2008-02-19.
  11. First Aid for the USMLE Step 1, 2010. Page 286.
  12. 12.0 12.1 Costoff A. "Sect. 5, Ch. 4: Structure, Synthesis, and Secretion of Somatostatin". Endocrinology: The Endocrine Pancreas. Medical College of Georgia. p. 17. Archived from the original on March 31, 2008. Retrieved 2008-02-19.
  13. Van der Meulen T, Donaldson CJ, Cáceres E, Hunter AE, Cowing-Zitron C, Pound LD, Adams MW, Zembrzycki A, Grove KL, Huising MO (2016-06-15). "Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion". Nature Medicine. 21: 769–76. doi:10.1038/nm.3872. PMC 4496282. PMID 26076035. Retrieved 2016-05-30.

Further reading