Somatostatin

Somatostatin

Somatostatin (also known as growth hormone inhibiting hormone (GHIH) or somatotropin release-inhibiting factor (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 acids, the other of 28 amino acids.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 | authorlink = | coauthors = | date = | format = | work = Endocrinology: The Endocrine Pancreas | publisher = Medical College of Georgia | pages = page 16 | language = | archiveurl = | archivedate = | quote = ]

Production

Digestive system

Somatostatin is secreted in several locations in the digestive system:
* stomach
* intestine
* delta cells of the pancreascite book | author = Costanzo, Linda S. | title = Physiology | publisher = Lippincott Williams & Wilkins | location = Hagerstown, MD | year = 2003 | edition = 3rd edition | pages = page 280 | isbn = 0-7817-3919-5 | oclc = | doi = ]

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 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, the hippocampus and the brainstem nucleus of the solitary tract.

Actions

Somatostatin is classified as an inhibitory hormone, whose actions are spread to different parts of the body:

Anterior pituitary

In the anterior pituitary gland, the effects of somatostatin are:
* Inhibit the release of growth hormone (GH)cite web | url = http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/otherendo/somatostatin.html | title = Somatostatin | accessdate = 2008-02-19 | author = Bowen R | authorlink = | coauthors = | date = 2002-12-14 | format = | work = Biomedical Hypertextbooks | publisher = Colorado State University | pages = | language = | archiveurl = | archivedate = | quote = ] (thus opposing the effects of Growth Hormone-Releasing Hormone (GHRH))
* Inhibit the release of thyroid-stimulating hormone (TSH)

Gastrointestinal system

* Somatostatin suppresses the release of gastrointestinal hormones
** Gastrin
** Cholecystokinin (CCK)
** Secretin
** Motilin
** Vasoactive intestinal peptide (VIP)
** Gastric inhibitory polypeptide (GIP)
** Enteroglucagon
* Lowers the rate of gastric emptying, and reduces smooth muscle contractions and blood flow within the intestine
* Suppresses the release of pancreatic hormones
** Inhibits the release of insulincite 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 | authorlink = | coauthors = | date = | format = | work = Endocrinology: The Endocrine Pancreas | publisher = Medical College of Georgia | pages = page 17 | language = | archiveurl = | archivedate = | quote = ]
** Inhibits the release of glucagon
* Suppresses the exocrine secretory action of pancreas.

ynthetic substitutes

Octreotide (brand name "Sandostatin", Novartis Pharmaceuticals) is an octopeptide that mimics natural somatostatin pharmacologically, though is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone.

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=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 | author=Yamada Y, Reisine T, Law SF, "et al." |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=
*cite journal | author=Yamada Y, Post SR, Wang K, "et al." |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
*cite journal | author=Brazeau P, Vale W, Burgus R, "et al." |title=Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone |journal=Science |volume=179 |issue= 68 |pages= 77–9 |year= 1973 |pmid= 4682131| doi=10.1126/science.179.4068.77
*cite journal | author=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
*cite journal | author=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 | author=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
*cite journal | author=Zabel BU, Naylor SL, Sakaguchi AY, "et al." |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=
*cite journal | author=Panetta R, Greenwood MT, Warszynska A, "et al." |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 | author=Demchyshyn LL, Srikant CB, Sunahara RK, "et al." |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 | author=Kaupmann K, Bruns C, Hoyer D, "et al." |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 | author=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 | author=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=
*cite journal | author=Dournaud P, Boudin H, Schonbrunn A, "et al." |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 | author=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 | author=Ferone D, van Hagen PM, van Koetsveld PM, "et al." |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=
*cite journal | author=Brakch N, Lazar N, Panchal M, "et al." |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 | author=Oomen SP, van Hennik PB, Antonissen C, "et al." |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 | author=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

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