Somatostatins

Somatostatins are peptide hormones that broadly inhibit the secretion and activity of many other hormones and exocrine fluids. The two main biologically active forms are somatostatin-14 and somatostatin-28, produced by proteolytic processing of the SST gene. They are released in the central nervous system and in peripheral tissues, including the hypothalamus, gastrointestinal tract, and pancreas. In the hypothalamus, somatostatin is released into portal vessels to regulate pituitary hormone secretion; it also acts locally as a paracrine regulator in several tissues.

Somatostatins exert their effects by binding to somatostatin receptors, of which five subtypes (SSTR1–SSTR5) have been identified. These G protein–coupled receptors inhibit adenylyl cyclase via Gi/o signaling, reducing intracellular cAMP, opening potassium channels, and inhibiting voltage-gated calcium channels. This results in decreased secretion of various hormones, notably growth hormone and thyroid-stimulating hormone, as well as insulin and glucagon. In the gastrointestinal tract, somatostatins suppress the release of gastrin, cholecystokinin, secretin, vasoactive intestinal peptide, motilin, and other factors, and they slow motility and exocrine secretions.

Physiologically, somatostatins regulate endocrine and neuroendocrine signaling, gastrointestinal function, and neuronal communication. Clinically, synthetic analogs such as octreotide, lanreotide, and pasireotide are used to treat conditions including acromegaly, gastroenteropancreatic neuroendocrine tumors, and certain hormone-secreting tumors; they also help control symptoms in VIPoma and carcinoid syndrome and may be used in diagnostic suppression tests. Common side effects include gastrointestinal symptoms, gallstones, and glucose intolerance.