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 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. Alternate cleavage sites of the SST preproprotein results in the production of the hormone Neuronostatin, which has two active forms as Neuronostatin-13 and Neuronostatin-19. Neuronostatin is distinct from Somatostatin in its amino acid sequence, post-translation modifications and receptor binding.
Among the vertebrates, there exist six different somatostatin genes that have been named: SS1, SS2, SS3, SS4, SS5 and SS6. Zebrafish have all six.
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 manner. the hippocampus, and the brainstem nucleus of the solitary tract.
Functions
thumb|350px|[[D cell (biology)|D cell is visible at upper right, and somatostatin is represented by middle arrow pointing left]]
Somatostatin is classified as an inhibitory hormone,
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
- Inhibits the release of glucagon 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. 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.