Somatostatin
Also known as: growth hormone-inhibiting hormone, GHIH, SRIF, somatotropin release-inhibiting factor
An inhibitory peptide made by the hypothalamus, pancreatic δ cells and gut D cells that suppresses GH and TSH release, insulin and glucagon secretion, and most gastrointestinal secretion and motility.
Overview
Somatostatin exists as two active forms cleaved from one precursor: SST-14 (predominant in hypothalamus and islets) and SST-28 (predominant in the gut). In the hypothalamus it is secreted by periventricular neurons into portal blood and inhibits GH (and TSH) release from the anterior pituitary. In the pancreatic islets, δ cells release it as a local paracrine brake on α and β cells. In the stomach and intestine, D cells release it in response to luminal acid, inhibiting gastrin, histamine and acid secretion — the main negative-feedback loop of gastric acid.
All five receptors (SSTR1–5) are Gi-coupled GPCRs that lower cAMP, open K⁺ channels and close Ca²⁺ channels, thereby inhibiting exocytosis — hence its role as a "universal off switch". Its plasma half-life is only 1–3 minutes, so stable analogues were developed for therapy.
- Location
Sources: periventricular nucleus of the hypothalamus; pancreatic δ cells; gastric and intestinal D cells; enteric neurons. Targets: somatotrophs and thyrotrophs; α and β cells; parietal, G and ECL cells; exocrine pancreas and gut smooth muscle.
Function
- Inhibits GH and TSH secretion.
- Inhibits insulin and glucagon release (paracrine).
- Inhibits gastrin, gastric acid, pancreatic exocrine secretion, gallbladder contraction and nutrient absorption.
- Reduces splanchnic blood flow.
- Physiology
Class: peptide (14 and 28 amino acids). Receptors: SSTR1–5, Gi (↓cAMP, ↑K⁺ conductance, ↓Ca²⁺ entry). Half-life ≈1–3 min.
- Regulation
Hypothalamic release is stimulated by GH and IGF-1 (feedback); gastric D cells by luminal acid (pH <3) and gastrin; δ cells by glucose, amino acids and GLP-1.
Clinical significance
Somatostatin analogues
Octreotide and lanreotide (and pasireotide) bind SSTR2/5: used in acromegaly, TSH-omas, neuroendocrine (carcinoid) tumours and VIPomas, and to reduce portal pressure in bleeding oesophageal varices. Side effects: gallstones, steatorrhoea, hyperglycaemia. Radiolabelled analogues (⁶⁸Ga-DOTATATE PET) image neuroendocrine tumours.
Somatostatinoma
Rare pancreatic/duodenal tumour causing the inhibitory syndrome of diabetes, cholelithiasis, steatorrhoea and achlorhydria.
Compiled from standard anatomy and physiology references — see the Endocrine System sources. For education only; not medical advice.