Somatostatin (also known as growth
hormone-inhibiting hormone (GHIH)
or somatotropin
release-inhibiting factor (SRIF))
or somatotropin
release-inhibiting hormone[citation needed] is a peptide hormone that
regulates the endocrine system and affects neurotransmission and cell proliferationvia interaction with G-protein-coupled somatostatin receptors and
inhibition of the release of numerous secondary hormones.
Somatostatin
has two active forms produced by alternative cleavage of a single
preproprotein: one of 14 amino
acids, the other of 28 amino acids.[1]
In all vertebrates, there exists six different
somatostatin genes that have been named SS1, SS2, SS3, SS4, SS5, and SS6. [2] The six different genes along
with the five different somatostatin
receptors allows somatostatin to possess a large range of
functions.[3] Humans have only one somatostatin gene, SST.[4][5][6]
Production
Digestive system
Somatostatin
is secreted in several locations in the digestive system:
§
stomach
§
intestine
§ delta cells of the pancreas[7]
[Brain
Somatostatin
is produced by neuroendocrine neurons of
the periventricular
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[citation needed], thehippocampus[citation needed], and the
brainstem nucleus of the
solitary tract[citation needed].
Actions
Somatostatin
is classified as an inhibitory hormone,[1] whose
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)[8] (thus
opposing the effects of Growth
Hormone-Releasing Hormone (GHRH))
§ Inhibit the
release of thyroid-stimulating
hormone (TSH)[9]
§ It is
induced by low pH.
§ Inhibit
adenylyl cyclase in parietal cells.
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[8]
§ Suppresses
the release of pancreatic hormones
§ Inhibits
insulin release when somatostatin is released from delta cells of pancreas[10]
§ Inhibits the
release of glucagon[10]
§ Suppresses the
exocrine secretory action of pancreas.
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, acute variceal bleeding, and acromegaly. It is also finding increased
use in polycystic diseases of the liver and kidney.
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.
