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.["somatostatin". Encyclopædia Britannica. Encyclopædia Britannica Online. Encyclopædia Britannica Inc., 2016. Web. 04 mag. 2016 .]
Somatostatin has two active forms produced by the alternative cleavage of a single preproprotein: one consisting of 14 (shown in infobox to right), the other consisting of 28 amino acids.
Among the vertebrates, there exist six different somatostatin genes that have been named: SS1, SS2, SS3, SS4, SS5 and SS6.
Nomenclature
Synonyms of "somatostatin" include:
-
growth hormone–inhibiting hormone (GHIH)
-
growth hormone release–inhibiting hormone (GHRIH)
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somatotropin release–inhibiting factor (SRIF)
-
somatotropin release–inhibiting hormone (SRIH)
Production
Digestive system
Somatostatin is secreted by
delta cells at several locations in the digestive system, namely the
pyloric antrum, the
duodenum and the pancreatic islets.
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.
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.
Brain
| [File:Sst, is expressed in interneurons in the telencephalon of the embryonic day 15.5 mouse. Allen Brain Atlases]] | [File: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 hypothalamohypophysial 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, populations of somatostatin neurons occur in the arcuate nucleus,
Functions
Somatostatin is classified as an
inhibitory hormone,
and is induced by low pH. Its actions are spread to different parts of the body. Somatostatin release is inhibited by the
vagus nerve.
Anterior pituitary
In the anterior pituitary gland, the effects of somatostatin are:
-
Inhibiting the release of growth hormone (GH)
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Inhibiting the release of thyroid-stimulating hormone (TSH)
[First Aid for the USMLE Step 1, 2010. Page 286.]
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Inhibiting adenylyl cyclase in parietal cells
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Inhibiting the release of prolactin (PRL)
Gastrointestinal system
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Somatostatin is homologous with CORT (see somatostatin family) and suppresses the release of gastrointestinal hormones
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Decreases the rate of gastric emptying, and reduces smooth muscle contractions and blood flow within the intestine
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Suppresses the release of pancreatic hormones
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Somatostatin release is triggered by the beta cell peptide urocortin3 (Ucn3) to inhibit insulin release.
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Inhibits the release of glucagon
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Suppresses the exocrine secretory action of the pancreas
Synthetic substitutes
Octreotide (brand name Sandostatin,
Novartis) is an
peptide 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 (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 for symptomatic treatment of carcinoid syndrome and
acromegaly.
It is also finding increased use in polycystic diseases of the liver and kidney.
Lanreotide (Somatuline, Ipsen) 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 on August 30, 2007.
Pasireotide, sold under the brand name Signifor, is an orphan drug approved in the United States and the European Union for the treatment of Cushing's disease in patients who fail or are ineligible for surgical therapy. It was developed by Novartis. Pasireotide is somatostatin analog with a 40-fold increased affinity to somatostatin receptor 5 compared to other somatostatin analogs.
Evolutionary history
Six somatostatin genes 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.
See also
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FK962
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Hypothalamic–pituitary–somatic axis
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Octreotide
Further reading
External links
