The Discovery of Somatostatin
| Category | Research |
|---|---|
| Also known as | somatostatin history, Brazeau somatostatin, growth hormone inhibiting hormone |
| Last updated | 2026-04-14 |
| Reading time | 3 min read |
| Tags | historysomatostatinhypothalamic-hormonesgrowth-hormone |
Overview
Somatostatin is a cyclic 14-amino-acid peptide hormone that inhibits the secretion of growth hormone, insulin, glucagon, and many other hormones. It was identified in 1973 by Paul Brazeau, Roger Guillemin, and colleagues at the Salk Institute during systematic efforts to isolate hypothalamic factors controlling pituitary secretion.
Initial interest was driven by the long-standing hypothesis that the hypothalamus produces releasing and inhibiting factors that regulate the anterior pituitary. Guillemin's and Andrew Schally's laboratories had already isolated thyrotropin releasing hormone (TRH) and gonadotropin releasing hormone (GnRH). While searching for a growth hormone releasing factor, Brazeau's team instead isolated a peptide that strongly inhibited GH release — a discovery as important as any positive releasing factor.
Somatostatin is now known to exist in two main biologically active forms: somatostatin-14 (the original isolate) and somatostatin-28 (a larger N-terminally extended form). Both act through five G protein-coupled receptors, SSTR1 through SSTR5, with broad distribution in the brain, gastrointestinal tract, pancreas, and elsewhere.
Key People
- Paul Brazeau: First author of the 1973 paper reporting somatostatin's isolation.
- Roger Guillemin (1924–2024): French-American neuroendocrinologist and 1977 Nobel laureate.
- Andrew V. Schally: Polish-American neuroendocrinologist who shared the 1977 Nobel Prize.
- Wylie Vale: Student in Guillemin's lab who contributed to the work and later led significant neuropeptide research.
Timeline
- 1968–1972: Guillemin's lab pursues hypothalamic factors controlling growth hormone.
- 1973: Somatostatin-14 is isolated, sequenced, and synthesized.
- 1977: Guillemin and Schally share the Nobel Prize in Physiology or Medicine with Rosalyn Yalow.
- 1980: Somatostatin-28 is characterized.
- 1988: Octreotide is approved for acromegaly and neuroendocrine tumors.
- 1990s: Five somatostatin receptor subtypes are cloned.
Background
Guillemin and Schally competed fiercely for decades to isolate hypothalamic peptides. Each laboratory processed enormous quantities of hypothalamic tissue — reportedly millions of sheep hypothalami in Guillemin's case and nearly as many porcine hypothalami in Schally's — to obtain workable quantities of each factor. The rivalry was acrimonious but enormously productive, yielding the structures of TRH, GnRH, and ultimately somatostatin.
Somatostatin's broad inhibitory profile gave it immediate pharmacological interest. It inhibits secretion of growth hormone, insulin, glucagon, gastrin, cholecystokinin, secretin, and others. This makes full-length somatostatin unsuitable as a therapeutic, but it also created opportunities for designing more selective, stable analogs.
Modern Relevance
Somatostatin analogs are now mainstays of endocrine oncology. Octreotide and lanreotide are widely used to control acromegaly, carcinoid syndrome, and hormone secretion from pancreatic neuroendocrine tumors. Newer agents such as pasireotide have different receptor-subtype selectivity profiles and are used for Cushing disease and refractory acromegaly.
Beyond oncology, somatostatin signaling is explored in gastroenterology, ophthalmology, and neurology. Radiolabeled somatostatin analogs (DOTATATE, DOTATOC) underpin modern peptide receptor radionuclide therapy for neuroendocrine tumors, combining imaging and therapy in a single molecular platform. For broader context, see nobel-prize-hypothalamic-hormones.
Related Compounds
Related entries
- The Discovery of ACTH— ACTH, the pituitary peptide that drives cortisol release, was isolated and sequenced through efforts by Li, Bell, Harris, and others in the 1940s-1950s.
- History of Growth Hormone Research— An overview of the discovery, purification, and recombinant production of growth hormone over the twentieth century.
- The 1977 Nobel Prize for Hypothalamic Hormones— Roger Guillemin and Andrew Schally shared half of the 1977 Nobel Prize for isolating TRH, GnRH, and other hypothalamic peptide hormones.