Secretin: Physiology and What Research Reports

What Secretin Is

Secretin is a 27-amino-acid peptide hormone produced by enteroendocrine S cells in the mucosa of the duodenum and proximal jejunum. It occupies a unique place in endocrinology: it was the substance whose discovery established the concept of a hormone — a chemical messenger carried in the blood from one tissue to act on another — and a historical review described it as the first hormone (PMID 11816326).

Structurally, secretin belongs to the secretin/glucagon superfamily, which also contains glucagon, GLP-1, GIP, VIP, PACAP and growth hormone-releasing hormone. That family relationship is why secretin appears so often in peptide literature: many of the incretin and metabolic peptides that dominate modern research share its helical architecture and its class B G protein-coupled receptor fold.

This page is for educational purposes only and is not medical advice; consult a licensed physician for any question about health, diagnosis or treatment.

Where It Is Produced and What It Does

The classical trigger for secretin release is acid. When gastric chyme with a low pH enters the duodenum, S cells release secretin into the circulation. A 2024 physiology review framed secretin primarily as a hormone for bicarbonate homeostasis, describing how it stimulates HCO₃⁻ and fluid secretion from pancreatic duct epithelium and biliary epithelium so that duodenal contents are neutralised and pancreatic enzymes can work at a suitable pH (PMID 38221598).

At the cellular level, secretin binds the secretin receptor (SCTR), a class B GPCR. A review of secretin receptor signalling reported that receptor activation couples primarily to Gs and adenylyl cyclase, raising intracellular cAMP and activating protein kinase A, with additional described coupling to calcium-dependent pathways (PMID 16930743). In duct cells, the cAMP rise opens CFTR chloride channels and drives the chloride–bicarbonate exchange that produces the alkaline, watery pancreatic juice secretin is named for.

Beyond the pancreas

Secretin receptors have been mapped well outside the gut. A 2018 commentary in Cell reviewed evidence that secretin acts on brown adipose tissue, linking a classical digestive hormone to thermogenesis and meal-associated energy expenditure (PMID 30500531). Human imaging work extended this: a 2023 nuclear medicine study reported that secretin modulated appetite via a brown adipose tissue–brain axis (PMID 36764966).

Central actions have also been described in animals. A 2024 study in mice reported that secretin-dependent signals in the ventromedial hypothalamus regulated energy metabolism and bone homeostasis (PMID 38310104). Earlier work reported that secretin activated supraoptic oxytocin neurons and that this activation facilitated social recognition in rodents (PMID 26803341), and a separate mouse study reported that secretin attenuated hereditary repetitive hyperactive movements in a mouse model (PMID 20607447).

Motility is another described target. A 2025 report found that secretin acted on interstitial cells of Cajal — the pacemaker cells of the gut — to regulate intestinal contractions (PMID 41198902).

Summary of described actions

How Secretin Is Measured and Studied

Secretin is unusual among gut peptides in that a synthetic form is used diagnostically, so much of the human literature is imaging and provocative-testing literature rather than treatment literature.

Secretin-enhanced MR cholangiopancreatography

In secretin-stimulated MRCP, secretin is given intravenously to transiently increase pancreatic exocrine output, distending the pancreatic ductal system and improving its visualisation on MR images. A 2006 abdominal imaging review described secretin-stimulated MRCP as a method for improved depiction of pancreatic duct anatomy and for functional assessment of exocrine response (PMID 16465582). A companion radiology review described the dynamic form of the technique, in which sequential images after secretin administration are used to assess duct compliance, drainage and duodenal filling (PMID 16702446). Reported applications in these reviews included pancreas divisum, suspected chronic pancreatitis, and post-surgical or post-traumatic ductal evaluation.

Provocative testing in gastrinoma

Secretin also underpins a classical endocrine provocative test. In Zollinger–Ellison syndrome, gastrin-secreting tumours paradoxically increase gastrin release after secretin, whereas normal G cells do not. A 2007 study examined secretin-receptor and secretin-receptor-variant expression in gastrinomas and correlated expression with clinical and tumoral features and with secretin and calcium provocative test results (PMID 17711922).

Preclinical approaches

Animal and cell work in this literature used receptor knockouts, region-specific manipulation of secretin signalling in brain nuclei, and electrophysiological or contractility recordings. The ventromedial hypothalamus study used mice to dissect central secretin signals (PMID 38310104), while the interstitial cells of Cajal work assessed intestinal contraction directly (PMID 41198902).

Why Secretin Matters in Peptide Research

Three reasons recur. First, secretin is the archetype of the class B GPCR peptide, and understanding how it activates its receptor informs work on the whole glucagon/incretin family (PMID 16930743). Second, the brown adipose tissue findings reframed a digestive hormone as a metabolic and satiety signal, which is why it appears in energy-balance reviews (PMID 30500531, PMID 36764966). Third, its central actions on oxytocin neurons connect it to social behaviour neuroscience (PMID 26803341).

Readers may also encounter secretin in discussions of autism spectrum disorder, a topic that arose in the late 1990s from anecdotal reports after diagnostic secretin infusions. The verified literature summarised here does not include clinical trials in that population; the rodent behavioural findings above (PMID 20607447, PMID 26803341) are preclinical and do not establish human outcomes.

Secretin: What Studies Report

Because most human exposure in the cited literature is a single diagnostic intravenous administration, the reported experience is short-term. The imaging reviews described secretin administration during MRCP as a means to stimulate pancreatic exocrine output and duodenal filling, with the expected physiological consequence being increased fluid volume in the duodenum (PMID 16702446, PMID 16465582). In provocative testing, researchers used secretin specifically because it produces a measurable gastrin response in gastrinoma patients, and that study correlated test results with receptor and receptor-variant expression (PMID 17711922). The verified papers summarised on this page did not report a systematic adverse-event tabulation, so no safety profile is asserted here. Questions about tolerability of any clinical secretin product belong with a licensed physician and the product's own labelling.

References

• [Secretin—the first hormone] (Ugeskrift for laeger, 2002)
• Secretin: a hormone for HCO3- homeostasis (Pflugers Archiv, 2024)
• Signaling mechanisms of secretin receptor (Regulatory Peptides, 2006)
• Secretin: An Old Hormone with a Burning Secret (Cell, 2018)
• Secretin modulates appetite via brown adipose tissue-brain axis (European Journal of Nuclear Medicine and Molecular Imaging, 2023)
• Secretin-dependent signals in the ventromedial hypothalamus regulate energy metabolism and bone homeostasis in mice (Nature Communications, 2024)
• Activation of Supraoptic Oxytocin Neurons by Secretin Facilitates Social Recognition (Biological Psychiatry, 2017)
• Secretin attenuates the hereditary repetitive hyperactive movements in a mouse model (Journal of Molecular Neuroscience, 2011)
• Secretin targets interstitial cells of Cajal to regulate intestinal contractions (EMBO Reports, 2025)
• Secretin-stimulated MRCP (Abdominal Imaging, 2006)
• Dynamic secretin-enhanced MR cholangiopancreatography (RadioGraphics, 2006)
• Secretin-receptor and secretin-receptor-variant expression in gastrinomas (Journal of Clinical Endocrinology and Metabolism, 2007)