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Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the
endocrine system The endocrine system is a messenger system in an organism comprising feedback loops of hormones that are released by internal glands directly into the circulatory system and that target and regulate distant Organ (biology), organs. In vertebrat ...
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 has two active forms produced by the alternative cleavage of a single preproprotein: one consisting of 14 amino acids (shown in infobox to right), the other consisting of 28 amino acids. Among the
vertebrates Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...
, there exist six different somatostatin genes that have been named: ''SS1'', ''SS2'', ''SS3'', ''SS4'', ''SS5'' and ''SS6''. Zebrafish have all six. The six different genes, along with the five different somatostatin receptors, allow somatostatin to possess a large range of functions. Humans have only one somatostatin gene, ''SST''.


Nomenclature

Synonyms of "somatostatin" include: * growth hormone–inhibiting hormone (GHIH) * growth hormone release–inhibiting hormone (GHRIH) * 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 In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication (biology), cellular communication in which a Cell (biology), cell produces a signal to induce changes in nearby cells, altering the behaviour of ...
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. Somatostatin can also indirectly decrease stomach acid production by preventing the release of other hormones, including gastrin and
histamine Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 19 ...
which effectively slows down the digestive process.


Brain

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, the
hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...
, and the brainstem nucleus of the solitary tract.


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 The vagus nerve, also known as the tenth cranial nerve (CN X), plays a crucial role in the autonomic nervous system, which is responsible for regulating involuntary functions within the human body. This nerve carries both sensory and motor fibe ...
.


Anterior pituitary

In the anterior pituitary gland, the effects of somatostatin are: * Inhibiting the release of growth hormone (GH) (thus opposing the effects of growth hormone–releasing hormone (GHRH)) * Inhibiting the release of thyroid-stimulating hormone (TSH) * Inhibiting adenylyl cyclase in parietal cells * Inhibiting the release of prolactin (PRL)


Gastrointestinal system

* Somatostatin is homologous with cortistatin (see somatostatin family) and suppresses the release of gastrointestinal hormones * Decreases the rate of gastric emptying, and reduces smooth muscle contractions and blood flow within the intestine * Suppresses the release of pancreatic hormones ** Somatostatin release is triggered by the beta cell peptide urocortin3 (Ucn3) to inhibit
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...
release. ** Inhibits the release of glucagon * Suppresses the exocrine secretory action of the 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 Half-life is a mathematical and scientific description of exponential or gradual decay. Half-life, half life or halflife may also refer to: Film * Half-Life (film), ''Half-Life'' (film), a 2008 independent film by Jennifer Phang * ''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 Pharmaceuticals) 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 Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...
. 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 Sarcopterygii (; )—sometimes considered synonymous with Crossopterygii ()—is a clade (traditionally a class (biology), class or subclass) of vertebrate animals which includes a group of bony fish commonly referred to as lobe-finned fish. The ...
and
Actinopterygii Actinopterygii (; ), members of which are known as ray-finned fish or actinopterygians, is a class (biology), class of Osteichthyes, bony fish that comprise over 50% of living vertebrate species. They are so called because of their lightly built ...
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

* FK962 * Hypothalamic–pituitary–somatic axis * Octreotide


References


Further reading

* * * * * * * * * * * * * * * * * * *


External links

* {{GH/IGF-1 axis signaling modulators Antidiarrhoeals Endocrine system Hormones of the somatotropic axis Neuropeptides Neuroendocrinology Pancreatic hormones Somatostatin inhibitors