Somatostatin

SST
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2MI1
Identifiers
Aliases	SST, SMST, somatostatin, Somatostatin
External IDs	OMIM: 182450 MGI: 98326 HomoloGene: 819 GeneCards: SST
Gene ontology Molecular function • hormone activity Cellular component • extracellular region • extracellular fluid • neuronal cell body Biological process • negative regulation of cell proliferation • hormone-mediated apoptotic signaling pathway • hyperosmotic response • chemical synaptic transmission • regulation of cell migration • response to heat • response to nutrient • response to acidic pH • response to drug • response to steroid hormone • G-protein coupled receptor signaling pathway • response to amino acid • cell-cell signaling • response to organonitrogen compound • digestion • cell surface receptor signaling pathway Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6750	20604
Ensembl	ENSG00000157005	ENSMUSG00000004366
UniProt	P61278	P60041
RefSeq (mRNA)	NM_001048	NM_009215
RefSeq (protein)	NP_001039.1	NP_033241.1
Location (UCSC)	Chr 3: 187.67 – 187.67 Mb	Chr 16: 23.89 – 23.89 Mb
PubMed search	[1]	[2]
Wikidata

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.^[3]

Somatostatin has two active forms produced by alternative cleavage of a single preproprotein: one of 14 amino acids (shown in infobox to right), the other of 28 amino acids^[4] which is the short form with another 14 amino acids at one end.^[5]

Among the vertebrates, there exist six different somatostatin genes that have been named SS1, SS2, SS3, SS4, SS5, and SS6.^[6] Zebrafish have all 6.^[6] The six different genes along with the five different somatostatin receptors allows somatostatin to possess a large range of functions.^[7] Humans have only one somatostatin gene, SST.^[8][9][10]

Nomenclature

Synonyms of somatostatin are as follows:

• 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 at several locations in the digestive system:

• Delta cells in the pyloric antrum, the duodenum and the pancreatic islets^[11]

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.^[11]

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.^[11] Somatostatin can also indirectly decrease stomach acid production by preventing the release of other hormones, including gastrin, secretin and histamine which effectively slows down the digestive process.

Brain

Sst is expressed in interneurons in the telencephalon of the embryonic day 15.5 mouse. Allen Brain Atlases

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 hypothalamo-hypophysial 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, there are populations of somatostatin neurons in the arcuate nucleus, the hippocampus, and the brainstem nucleus of the solitary tract.

Actions

D cell is visible at upper-right, and somatostatin is represented by middle arrow pointing left

Somatostatin is classified as an inhibitory hormone,^[4] and is induced by low pH.. Its actions are spread to different parts of the body.

Anterior pituitary

In the anterior pituitary gland, the effects of somatostatin are:

• Inhibit the release of growth hormone (GH)^[12] (thus opposing the effects of growth hormone–releasing hormone (GHRH))
• Inhibit the release of thyroid-stimulating hormone (TSH)^[13]
• Inhibit adenylyl cyclase in parietal cells.
• Inhibits the release of prolactin (PRL)

Gastrointestinal system

• Somatostatin is homologous with cortistatin (see somatostatin family) and suppresses the release of gastrointestinal hormones
  • Gastrin
  • Cholecystokinin (CCK)
  • Secretin
  • Motilin
  • Vasoactive intestinal peptide (VIP)
  • Gastric inhibitory polypeptide (GIP)
  • Enteroglucagon
• Decrease rate of gastric emptying, and reduces smooth muscle contractions and blood flow within the intestine^[12]
• Suppresses the release of pancreatic hormones
  • Somatostatin release is triggered by the beta cell peptide Urocortin3 (Ucn3) to attenuate further insulin release in negative feedback fashion^[14][15]
  • Inhibits the release of glucagon^[14]
• Suppresses the exocrine secretory action of 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 (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 symptomatic treatment of carcinoid syndrome and acromegaly. It is also finding increased use in polycystic diseases of the liver and kidney.

Lanreotide (brand name 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 (FDA) on August 30, 2007.

Evolutionary history

There are six somatostatin genes that 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.^[6]

References

Further reading