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approvedGI & Metabolic

Secretin

Also known as: SecreFlo, ChiRhoStim, Human Secretin

Secretin is a 27-amino-acid peptide hormone produced by S-cells of the duodenum, historically significant as the first hormone ever discovered (Bayliss and Starling, 1902). It is released in response to acidic chyme entering the duodenum and stimulates pancreatic bicarbonate and water secretion to neutralize gastric acid. FDA-approved as a diagnostic agent (SecreFlo, ChiRhoStim), secretin is used in pancreatic function testing and to diagnose gastrinoma (Zollinger-Ellison syndrome). It also plays emerging roles in neuroscience research as a potential modulator of social behavior and autism spectrum features.

3 cited references·5 researched benefits

Quick Answer

Secretin is a 27-amino-acid GI hormone and the first hormone ever discovered (1902). Produced by duodenal S-cells in response to gastric acid, it stimulates pancreatic bicarbonate secretion to neutralize stomach acid. FDA-approved as a diagnostic agent for pancreatic function testing and gastrinoma (Zollinger-Ellison syndrome) diagnosis. Research has explored its potential neurological effects, though controlled trials have not confirmed benefits for autism spectrum disorder.

Key Facts

Mechanism
Secretin is released from duodenal S-cells when luminal pH drops below 4.5 (acidic chyme from the stomach). It binds the secretin receptor (SCTR), a class B GPCR on pancreatic duct epithelial cells, activating Gs-cAMP-PKA signaling that opens CFTR chloride channels and stimulates bicarbonate-rich fluid secretion (up to 1–2 L/day). Secretin also inhibits gastric acid secretion (negative feedback), stimulates hepatic bile flow (choleresis), and potentiates CCK-stimulated pancreatic enzyme secretion. In the brain, secretin receptors are expressed in the cerebellum, hippocampus, and hypothalamus, where secretin modulates synaptic plasticity, water homeostasis (via vasopressin regulation), and social behavior circuits.
Research Status
approved
Half-Life
~2.5 minutes
Molecular Formula
C₁₃₀H₂₂₀N₄₄O₃₉
Primary Use
GI & Metabolic
Table of Contents

Benefits

  • Pancreatic function diagnosis — secretin stimulation test is the gold standard for detecting chronic pancreatitis and exocrine pancreatic insufficiencystrong
  • Gastrinoma localization — secretin provocation test differentiates Zollinger-Ellison syndrome from other causes of hypergastrinemia (diagnostic sensitivity ~85–95%)strong
  • MRCP enhancement — secretin-enhanced magnetic resonance cholangiopancreatography improves visualization of pancreatic duct anatomy and functionstrong
  • Pancreatic bicarbonate secretion — essential physiological role in neutralizing gastric acid to protect duodenal mucosa and optimize digestive enzyme activitystrong
  • Neuropeptide research — preclinical evidence of modulation of social behavior, water homeostasis, and cerebellar function through central secretin receptorspreliminary

Dosage Protocols

RouteDosage RangeFrequencyNotes
Intravenous (pancreatic function test)0.2 mcg/kgSingle doseAdministered as slow IV bolus over 1 minute. Duodenal aspirates collected at baseline and every 15 minutes for 60 minutes to measure bicarbonate concentration and volume. Peak bicarbonate >80 mEq/L is normal.
Intravenous (gastrinoma/ZES diagnosis)0.4 mcg/kg (2 CU/kg)Single doseSerum gastrin levels measured at baseline and 2, 5, 10, 15, 20, and 30 minutes post-injection. A rise in serum gastrin >120 pg/mL is highly suggestive of gastrinoma.
Intravenous (secretin-enhanced MRCP)0.2 mcg/kgSingle dose during imagingAdministered during MRCP to distend the pancreatic duct system, improving visualization of duct anatomy, side branches, and pancreatic exocrine function.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Abdominal discomfort — mild cramping or fullness during secretin stimulation testingcommon
  • Nausea — transient nausea during or immediately after IV administrationcommon
  • Flushing — brief vasodilatory flushing in some patientscommon
  • Allergic reactions — rare anaphylaxis; test dose recommended for patients with history of atopy or prior secretin exposureserious

Frequently Asked Questions

Why is secretin historically important?
Secretin was the first substance ever identified as a hormone. In 1902, William Bayliss and Ernest Starling demonstrated that an extract from the duodenal mucosa, when injected intravenously into dogs, stimulated pancreatic secretion — proving that chemical messengers (not just nerves) could coordinate organ function. Starling coined the word "hormone" (from Greek "to excite") to describe this new class of signaling molecules. This discovery founded the entire field of endocrinology.
Does secretin help with autism?
In 1998, a case report of three children with autism showing behavioral improvements after secretin infusion generated intense interest and media attention. However, subsequent rigorous randomized controlled trials (>15 studies) consistently failed to demonstrate significant benefit of secretin for autism spectrum disorder symptoms. The American Academy of Pediatrics and other bodies do not recommend secretin for autism. The initial findings were likely placebo effects and highlights the importance of controlled trials over case reports.
What is the secretin stimulation test for Zollinger-Ellison syndrome?
In normal individuals, IV secretin either decreases or does not change serum gastrin levels. In patients with gastrinomas (Zollinger-Ellison syndrome), secretin paradoxically stimulates a dramatic increase in gastrin release (>120 pg/mL rise from baseline within 2–10 minutes). This occurs because gastrinoma cells express secretin receptors that directly stimulate gastrin release, unlike normal G-cells. The test has ~85–95% sensitivity and >95% specificity for gastrinoma, making it the best provocative test for ZES diagnosis.
How is synthetic secretin different from porcine secretin?
Historically, porcine (pig-derived) secretin was used for diagnostic testing, but supply issues and rare allergic reactions led to the development of synthetic human secretin. SecreFlo (synthetic human secretin) was FDA-approved in 2004 and has the identical 27-amino-acid sequence as native human secretin. It is produced by solid-phase peptide synthesis, eliminating animal-derived product risks. ChiRhoStim is another synthetic human secretin preparation. Both are bioequivalent and produce identical physiological responses.

References

  1. 1
    Secretin: a new concept of its gastrointestinal function and clinical relevance(1998)PubMed ↗
  2. 2
    Secretin as a neuropeptide: distribution, receptors, and neurobiological functions(2006)PubMed ↗
  3. 3
    Secretin stimulation test for diagnosis of Zollinger-Ellison syndrome: systematic review and meta-analysis(2012)PubMed ↗

Latest Research

Last updated: 2026-02-19