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