Somatostatin

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Somatostatin
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Identifiers
Symbols	SST; SMST
External IDs	OMIM: 182450 MGI: 98326 HomoloGene: 819 GeneCards: SST Gene
Gene Ontology Molecular function • hormone activity Cellular component • extracellular region • extracellular space Biological process • G-protein coupled receptor protein signaling pathway • synaptic transmission • response to nutrient • digestion • negative regulation of cell proliferation • induction of apoptosis by hormones • regulation of cell migration Sources: Amigo / EGO
RNA expression pattern
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More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6750	20604
Ensembl	ENSG00000157005	ENSMUSG00000004366
UniProt	P61278	Q545V6
RefSeq (mRNA)	NM_001048	NM_009215
RefSeq (protein)	NP_001039	NP_033241
Location (UCSC)	Chr 3: 188.87 - 188.87 Mb	Chr 16: 23.8 - 23.81 Mb
PubMed search	[1]	[2]

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.

Production

Digestive system

Somatostatin is secreted in several locations in the digestive system:

• stomach
• intestine
• delta cells of the pancreas

Brain

Somatostatin is produced by neuroendocrine neurons of the paraventricular 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

File:Control-of-stomach-acid-sec.png

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

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) (thus opposing the effects of Growth Hormone-Releasing Hormone (GHRH))
• Inhibit the release of thyroid-stimulating hormone (TSH)
• It is induced by low pH.
• Secreted by "D" cells and alpha cells in Islet of Langerhans.
• Inhibit adenylyl cyclase in parietal cells.

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 insulin release when somatostatin is released from granules in delta cells of pancreatic islet of Langerhans cells
  • Inhibits the release of glucagon
• Suppresses the exocrine secretory action of pancreas.

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, acute variceal bleeding, and acromegaly. It is also finding increased use in polycystic diseases of the liver and kidney.

Lanreotide (INN) is a medication used in the management of acromegaly and symptoms caused by neuroendocrine tumors, most notably carcinoid syndrome. It is a long-acting analogue of somatostatin, like octreotide.

Lanreotide(as lanreotide acetate) is manufactured by Ipsen, and marketed under the trade name Somatuline. 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.

Further reading

• Florio T, Schettini G (2002). "[Somatostatin and its receptors. Role in the control of cell proliferation]". Minerva Endocrinol. 26 (3): 91–102. PMID 11753230. 
• Yamada Y, Reisine T, Law SF; et al. (1993). "Somatostatin receptors, an expanding gene family: cloning and functional characterization of human SSTR3, a protein coupled to adenylyl cyclase". Mol. Endocrinol. 6 (12): 2136–42. doi:10.1210/me.6.12.2136. PMID 1337145. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Yamada Y, Post SR, Wang K; et al. (1992). "Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney". Proc. Natl. Acad. Sci. U.S.A. 89 (1): 251–5. doi:10.1073/pnas.89.1.251. PMC 48214 Freely accessible. PMID 1346068. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Brazeau P, Vale W, Burgus R; et al. (1973). "Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone". Science. 179 (68): 77–9. doi:10.1126/science.179.4068.77. PMID 4682131. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Shen LP, Pictet RL, Rutter WJ (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 Freely accessible. PMID 6126875. CS1 maint: Multiple names: authors list (link)
• Shen LP, Rutter WJ (1984). "Sequence of the human somatostatin I gene". Science. 224 (4645): 168–71. doi:10.1126/science.6142531. PMID 6142531. 
• Montminy MR, Goodman RH, Horovitch SJ, Habener JF (1984). "Primary structure of the gene encoding rat preprosomatostatin". Proc. Natl. Acad. Sci. U.S.A. 81 (11): 3337–40. doi:10.1073/pnas.81.11.3337. PMC 345502 Freely accessible. PMID 6145156. CS1 maint: Multiple names: authors list (link)
• Zabel BU, Naylor SL, Sakaguchi AY; et al. (1984). "High-resolution chromosomal localization of human genes for amylase, proopiomelanocortin, somatostatin, and a DNA fragment (D3S1) by in situ hybridization". Proc. Natl. Acad. Sci. U.S.A. 80 (22): 6932–6. doi:10.1073/pnas.80.22.6932. PMC 390100 Freely accessible. PMID 6196780. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Panetta R, Greenwood MT, Warszynska A; et al. (1994). "Molecular cloning, functional characterization, and chromosomal localization of a human somatostatin receptor (somatostatin receptor type 5) with preferential affinity for somatostatin-28". Mol. Pharmacol. 45 (3): 417–27. PMID 7908405. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Demchyshyn LL, Srikant CB, Sunahara RK; et al. (1993). "Cloning and expression of a human somatostatin-14-selective receptor variant (somatostatin receptor 4) located on chromosome 20". Mol. Pharmacol. 43 (6): 894–901. PMID 8100352. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Kaupmann K, Bruns C, Hoyer D; et al. (1993). "Distribution and second messenger coupling of four somatostatin receptor subtypes expressed in brain". FEBS Lett. 331 (1-2): 53–9. doi:10.1016/0014-5793(93)80296-7. PMID 8405411. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Aguila MC, Rodriguez AM, Aguila-Mansilla HN, Lee WT (1996). "Somatostatin antisense oligodeoxynucleotide-mediated stimulation of lymphocyte proliferation in culture". Endocrinology. 137 (5): 1585–90. doi:10.1210/en.137.5.1585. PMID 8612489. CS1 maint: Multiple names: authors list (link)
• Sharma K, Patel YC, Srikant CB (1997). "Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3". Mol. Endocrinol. 10 (12): 1688–96. doi:10.1210/me.10.12.1688. PMID 8961277. CS1 maint: Multiple names: authors list (link)
• Dournaud P, Boudin H, Schonbrunn A; et al. (1998). "Interrelationships between somatostatin sst2A receptors and somatostatin-containing axons in rat brain: evidence for regulation of cell surface receptors by endogenous somatostatin". J. Neurosci. 18 (3): 1056–71. PMID 9437026. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Barnea A, Roberts J, Ho RH (1999). "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". Brain Res. 815 (2): 349–57. doi:10.1016/S0006-8993(98)01098-1. PMID 9878821. CS1 maint: Multiple names: authors list (link)
• Ferone D, van Hagen PM, van Koetsveld PM; et al. (1999). "In vitro characterization of somatostatin receptors in the human thymus and effects of somatostatin and octreotide on cultured thymic epithelial cells". Endocrinology. 140 (1): 373–80. doi:10.1210/en.140.1.373. PMID 9886848. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Brakch N, Lazar N, Panchal M; et al. (2002). "The somatostatin-28(1-12)-NPAMAP sequence: an essential helical-promoting motif governing prosomatostatin processing at mono- and dibasic sites". Biochemistry. 41 (5): 1630–9. doi:10.1021/bi011928m. PMID 11814357. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Oomen SP, van Hennik PB, Antonissen C; et al. (2002). "Somatostatin is a selective chemoattractant for primitive (CD34(+)) hematopoietic progenitor cells". Exp. Hematol. 30 (2): 116–25. doi:10.1016/S0301-472X(01)00772-X. PMID 11823046. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Simonetti M, Di BC (2002). "Structural motifs in the maturation process of peptide hormones. The somatostatin precursor. I. A CD conformational study". J. Pept. Sci. 8 (2): 66–79. doi:10.1002/psc.370. PMID 11860030. 

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