Somatostatin

(also known as growth-hormone-inhibiting hormone)

Somatostatin (also known as growth hormone-inhibiting hormone (GHIH) or somatotropin release-inhibiting factor (SRIF)) or somatotropin release-inhibiting hormone is a is_associated_with::peptide hormone that regulates the is_associated_with::endocrine system and affects is_associated_with::neurotransmission and is_associated_with::cell proliferation via interaction with is_associated_with::G protein-coupled is_associated_with::somatostatin receptors and inhibition of the release of numerous secondary hormones. Somatostatin inhibits insulin and glucagon secretion.

Somatostatin has two active forms produced by alternative cleavage of a single preproprotein: one of 14 is_associated_with::amino acids (shown in infobox to right), the other of 28 amino acids which is the short form with another 14 amino acids at one end.

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

Digestive system
Somatostatin is secreted at several locations in the digestive system:
 * is_associated_with::D cells in the is_associated_with::pyloric antrum, and the is_associated_with::duodenum
 * is_associated_with::delta cells of the pancreatic is_associated_with::islets of Langerhans

Somatostatin released in the is_associated_with::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 released from D cells can act in a is_associated_with::paracrine manner.

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

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

Actions


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

Anterior pituitary
In the is_associated_with::anterior pituitary gland, the effects of somatostatin are:
 * Inhibit the release of is_associated_with::growth hormone (GH) (thus opposing the effects of is_associated_with::growth hormone-releasing hormone (GHRH))
 * Inhibit the release of is_associated_with::thyroid-stimulating hormone (TSH)
 * It is induced by low pH.
 * Inhibit adenylyl cyclase in parietal cells.
 * Inhibits the release of prolactin (PRL)

Gastrointestinal system

 * Somatostatin is homologous with cortistatin (see is_associated_with::somatostatin family) and suppresses the release of is_associated_with::gastrointestinal hormones
 * is_associated_with::Gastrin
 * is_associated_with::Cholecystokinin (CCK)
 * is_associated_with::Secretin
 * is_associated_with::Motilin
 * is_associated_with::Vasoactive intestinal peptide (VIP)
 * is_associated_with::Gastric inhibitory polypeptide (GIP)
 * is_associated_with::Enteroglucagon
 * Decrease rate of gastric emptying, and reduces smooth muscle contractions and blood flow within the intestine
 * Suppresses the release of pancreatic hormones
 * Inhibits is_associated_with::insulin release when somatostatin is released from delta cells of pancreas
 * Inhibits the release of is_associated_with::glucagon
 * Suppresses the exocrine secretory action of is_associated_with::pancreas.

Synthetic substitutes
is_associated_with::Octreotide (brand name Sandostatin, Novartis Pharmaceuticals) is an octapeptide that mimics natural somatostatin pharmacologically, though is a more potent inhibitor of is_associated_with::growth hormone, glucagon, and is_associated_with::insulin than the natural hormone and has a much longer is_associated_with::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 is_associated_with::symptomatic treatment of is_associated_with::carcinoid syndrome and is_associated_with::acromegaly. It is also finding increased use in polycystic diseases of the liver and kidney.

is_associated_with::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.

is_associated_with::Lanreotide (as lanreotide acetate) is manufactured by is_associated_with::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.

Evolutionary history
There are six somatostatin genes that have been discovered in is_associated_with::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 is_associated_with::teleost fish. An ancestral somatostatin gene was duplicated during the first is_associated_with::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. is_associated_with::Tetrapods retained SS1 (also known as SS-14 and SS-28) and SS2 (also known as cortistatin) after the split in the is_associated_with::sarcopterygii and is_associated_with::actinopterygii lineage split. In is_associated_with::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.