Secretin: physiology, history, and clinical significance

Structure, secretion and receptor

Secretin is synthesised as a preprohormone in enteroendocrine S cells and processed to the mature peptide stored in secretory granules. Release is stimulated primarily by low pH in the proximal small intestine (acidic chyme) and by certain nutrients. Target tissues express the secretin receptor, a class B G protein‑coupled receptor that triggers cAMP‑mediated signalling when secretin binds.

Physiological actions

The classic actions of secretin are directed at protecting the intestinal lining and optimising digestion. Major effects include:

• Stimulation of pancreatic duct cells to secrete bicarbonate‑rich fluid, neutralising gastric acid in the duodenum.
• Promotion of biliary bicarbonate secretion and modulation of bile flow.
• Reduction of gastric acid secretion and slowing of gastric emptying.

Beyond the gut, secretin has roles in fluid and electrolyte homeostasis: studies since the 2000s indicate involvement in osmoregulation by influencing central and renal pathways, acting on the hypothalamus, pituitary gland, and kidney to help coordinate water balance and urine concentration.

Clinical applications and research

Secretin is used diagnostically in medicine. The secretin stimulation test assesses pancreatic exocrine function by provoking bicarbonate release; secretin-enhanced magnetic resonance cholangiopancreatography (MRCP) improves visualisation of pancreatic ducts. A number of experimental therapies and small studies have explored secretin's effects in non‑digestive conditions (for example, neuroendocrine signalling or behavioural disorders), but robust clinical applications beyond pancreatic and biliary diagnostics remain limited.

History and notable facts

Secretin holds an important place in science as the first hormone to be identified experimentally. Classic experiments performed in 1902 at University College London demonstrated that a blood‑borne substance released from the intestine stimulated pancreatic secretion; this work led to the broader concept of hormonal communication and to the coining of the term "hormone" a few years later. Ongoing research continues to refine understanding of secretin's central and peripheral roles, its receptor pharmacology, and potential therapeutic uses.