Somatostatin has two active forms produced by the alternative cleavage of a single preproprotein: one consisting of 14amino acids (shown in infobox to right), the other consisting of 28 amino acids.[7][8]
Among thevertebrates, there exist six different somatostatin genes that have been named:SS1,SS2,SS3,SS4,SS5 andSS6.[9]Zebrafish have all six.[9] The six different genes, along with the five differentsomatostatin receptors, allow somatostatin to possess a large range of functions.[10]Humans have only one somatostatin gene,SST.[11][12][13]
Somatostatin released in thepyloric 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 aparacrine manner.[14]
In the stomach, somatostatin acts directly on the acid-producingparietal cells via a G-protein coupled receptor (which inhibits adenylate cyclase, thus effectively antagonising the stimulatory effect of histamine) to reduce acid secretion.[14] Somatostatin can also indirectly decrease stomach acid production by preventing the release of other hormones, includinggastrin andhistamine which effectively slows down the digestive process.[citation needed]
Somatostatin is produced byneuroendocrine neurons of theventromedial nucleus of thehypothalamus. These neurons project to themedian eminence, where somatostatin is released from neurosecretory nerve endings into thehypothalamohypophysial system through neuron axons. Somatostatin is then carried to theanterior pituitary gland, where it inhibits the secretion ofgrowth hormone fromsomatotrope cells. The somatostatin neurons in the periventricular nucleus mediate negative feedback effects ofgrowth 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.[citation needed]
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, populations of somatostatin neurons occur in thearcuate nucleus,[15] thehippocampus,[16] and the brainstemnucleus of the solitary tract.[citation needed]
D cell is visible at upper right, and somatostatin is represented by middle arrow pointing left
Somatostatin is classified as aninhibitory hormone,[7] and is induced by low pH.[citation needed] Its actions are spread to different parts of the body. Somatostatin release is inhibited by thevagus nerve.[17]
Octreotide (brand name Sandostatin,Novartis Pharmaceuticals) is anoctapeptide 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 longerhalf-life (about 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 forsymptomatic treatment ofcarcinoid syndrome andacromegaly.[22][23] It is also finding increased use in polycystic diseases of the liver and kidney.
Lanreotide (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-actinganalog 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 on August 30, 2007.
Pasireotide, sold under the brand name Signifor, is anorphan drug approved in the United States and the European Union for the treatment ofCushing's disease in patients who fail or are ineligible for surgical therapy. It was developed byNovartis. Pasireotide is somatostatinanalog with a 40-fold increased affinity tosomatostatin receptor 5 compared to other somatostatin analogs.
Six somatostatin genes have been discovered invertebrates. 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 inteleost fish. An ancestral somatostatin gene was duplicated during the firstwhole-genome duplication event (1R) to createSS1 andSS2. 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 retainedSS1 (also known asSS-14 andSS-28) andSS2 (also known ascortistatin) after the split in theSarcopterygii andActinopterygii lineage split. Inteleost fish,SS1, SS2, andSS3 were duplicated during the third whole-genome duplication event (3R) to createSS1, SS2, SS4, SS5, and two genes that were lost during the evolution of teleost fish.SS1 andSS2 went through local duplications to give rise toSS6 andSS3.[9]
^abNelson DL, Cox M, Hoskins AA (2021).Lehninger Principles of Biochemistry (Eighth ed.). New York, NY: Macmillan Learning.ISBN978-1-319-22800-2.OCLC1243000176.The binding of somatostatin to its receptor in the pancreas leads to activation of aninhibitory G protein, or Gi, structurally homologous to Gs, that inhibits adenylyl cyclase and lowers [cAMP]. In this way, somatostatin inhibits the secretion of several hormones, including glucagon
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Brakch N, Lazar N, Panchal M, Allemandou F, Boileau G, Cohen P, et al. (February 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.PMID11814357.
Simonetti M, Di BC (February 2002). "Structural motifs in the maturation process of peptide hormones. The somatostatin precursor. I. A CD conformational study".Journal of Peptide Science.8 (2):66–79.doi:10.1002/psc.370.PMID11860030.S2CID20438890.
