Secretin is a hormone that both controls the environment in the duodenum by regulating secretions of the stomach and pancreas, and regulates water homeostasis throughout the body. It is produced in the S cells of the duodenum, which are located in the crypts of Lieberkühn. In humans, the secretin peptide is encoded by the SCT gene. Secretin was also the first hormone to be identified.
Secretin regulates the pH within the duodenum by inhibiting gastric acid secretion by the parietal cells of the stomach, and by stimulating bicarbonate production by the centroacinar cells and intercalated ducts of the pancreas. 
In 1902, William Bayliss and Ernest Starling were studying how the nervous system controls the process of digestion. It was known that the pancreas secreted digestive juices in response to the passage of food (chyme) through the pyloric sphincter into the duodenum. They discovered (by cutting all the nerves to the pancreas in their experimental animals) that this process was not, in fact, governed by the nervous system. They determined that a substance secreted by the intestinal lining stimulates the pancreas after being transported via the bloodstream. They named this intestinal secretion secretin. Secretin was the first such "chemical messenger" identified. This type of substance is now called a hormone, a term coined by Bayliss in 1905.
Secretin is initially synthesized as a 120 amino acid precursor protein known as prosecretin. This precursor contains an N-terminal signal peptide, spacer, secretin itself (residues 28–54), and a 72-amino acid C-terminal peptide.
The mature secretin peptide is a linear peptide hormone, which is composed of 27 amino acids and has a molecular weight of 3055. A helix is formed in the amino acids between positions 5 and 13. The amino acids sequences of secretin have some similarities to that of glucagon, vasoactive intestinal peptide (VIP), and gastric inhibitory peptide (GIP). Fourteen of 27 amino acids of secretin reside in the same positions as in glucagon, 7 the same as in VIP, and 10 the same as in GIP.
Secretin also has an amidated carboxyl-terminal amino acid which is valine. The sequence of amino acids in secretin is H–His-Ser-Asp-Gly-Thr-Phe-Thr-Ser-Glu-Leu-Ser-Arg-Leu-Arg-Asp-Ser-Ala-Arg-Leu-Gln-Arg-Leu-Leu-Gln-Gly-Leu-Val–NH2.
Secretin is released into circulation and/or intestinal lumen in response to low duodenal pH that ranges between 2 and 4.5 depending on species. Also, the secretion of secretin is increased by the products of protein digestion bathing the mucosa of the upper small intestine.
The acidity is due to hydrochloric acid in the chyme that enters the duodenum from the stomach via the pyloric sphincter. Secretin targets the pancreas, which causes the organ to secrete a bicarbonate-rich fluid that flows into the intestine. Bicarbonate ion is a base that neutralizes the acid, thus establishing a pH favorable to the action of other digestive enzymes in the small intestine and preventing acid burns. Other factors are involved in the release of secretin such as bile salts and fatty acids, which result in additional bicarbonates being added to the small intestine. Secretin release is inhibited by H2 antagonists, which reduce gastric acid secretion. As a result, if the pH in the duodenum increases above 4.5, secretin cannot be released.
Secretin increases watery bicarbonate solution from pancreatic and bile duct epithelium. Pancreatic centroacinar cells have secretin receptors in their plasma membrane. As secretin binds to these receptors, it stimulates adenylate cyclase activity and converts ATP to cyclic AMP. Cyclic AMP acts as second messenger in intracellular signal transduction and leads to increase in release of watery carbonate. It is known to promote the normal growth and maintenance of the pancreas.
Secretin increases water and bicarbonate secretion from duodenal Brunner's glands to buffer the incoming protons of the acidic chyme. It also enhances the effects of cholecystokinin to induce the secretion of digestive enzymes and bile from pancreas and gallbladder, respectively.
Although secretin releases gastrin from gastrinomas, it inhibits gastrin release from the normal stomach. It reduces acid secretion from the stomach by inhibiting gastrin release from G cells.:844 This helps neutralize the pH of the digestive products entering the duodenum from the stomach, as digestive enzymes from the pancreas (e.g., pancreatic amylase and pancreatic lipase) function optimally at slightly basic pH.
In addition, secretin stimulates pepsin secretion from chief cells, which can help break down proteins in food digestion. It stimulates release of glucagon, pancreatic polypeptide and somatostatin.
Secretin has been widely used in medical field especially in pancreatic functioning test because it increases pancreatic secretions. Secretin is either injected or given through a tube that is inserted through nose, stomach then duodenum. This test can provide information about whether there are any abnormalities in pancreas which can be gastrinoma, pancreatitis or pancreatic cancer.
Secretin modulates water and electrolyte transport in pancreatic duct cells, liver cholangiocytes, and epididymis epithelial cells. It is found to play a role in the vasopressin-independent regulation of renal water reabsorption.
Secretin is found in the magnocellular neurons of the paraventricular and supraoptic nuclei of the hypothalamus and along the neurohypophysial tract to neurohypophysis. During increased osmolality, it is released from the posterior pituitary. In the hypothalamus, it activates vasopressin release. It is also needed to carry out the central effects of angiotensin II. In the absence of secretin or its receptor in the gene knockout animals, central injection of angiotensin II was unable to stimulate water intake and vasopressin release.
It has been suggested that abnormalities in such secretin release could explain the abnormalities underlying type D syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH). In these individuals, vasopressin release and response are normal, although abnormal renal expression, translocation of aquaporin 2, or both are found. It has been suggested that "Secretin as a neurosecretory hormone from the posterior pituitary, therefore, could be the long-sought vasopressin independent mechanism to solve the riddle that has puzzled clinicians and physiologists for decades."
Food intake 
Secretin and its receptor are found in discrete nuclei of the hypothalamus, including the paraventricular nucleus and the arcuate nucleus, which are the primary brain sites for regulating body energy homeostasis. It was found that both central and peripheral injection of Sct reduce food intake in mouse, indicating a anorectic role of the peptide. This function of the peptide is mediated by the central melanocortin system.
See also 
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Further reading 
- Saus E, Brunet A, Armengol L et al. (2010). "Comprehensive copy number variant (CNV) analysis of neuronal pathways genes in psychiatric disorders identifies rare variants within patients". Journal of Psychiatric Research 44 (14): 971–978. doi:10.1016/j.jpsychires.2010.03.007. PMID 20398908.
- Bertenshaw GP, Turk BE, Hubbard SJ et al. (2001). "Marked differences between metalloproteases meprin A and B in substrate and peptide bond specificity". J. Biol. Chem. 276 (16): 13248–13255. doi:10.1074/jbc.M011414200. PMID 11278902.
- Lee LT, Lam IP, Chow BK (2008). "A functional variable number of tandem repeats is located at the 5' flanking region of the human secretin gene plays a downregulatory role in expression". J. Mol. Neurosci. 36 (1–3): 125–131. doi:10.1007/s12031-008-9083-5. PMID 18566919.
- Nussdorfer GG, BahÃ§elioglu M, Neri G, Malendowicz LK (2000). "Secretin, glucagon, gastric inhibitory polypeptide, parathyroid hormone, and related peptides in the regulation of the hypothalamus- pituitary-adrenal axis". Peptides 21 (2): 309–324. doi:10.1016/S0196-9781(99)00193-X. PMID 10764961.
- Lossi L, Bottarelli L, Candusso ME et al. (2004). "Transient expression of secretin in serotoninergic neurons of mouse brain during development". Eur. J. Neurosci. 20 (12): 3259–3269. doi:10.1111/j.1460-9568.2004.03816.x. PMID 15610158.
- Lee SM, Yung WH, Chen L, Chow BK (2005). "Expression and spatial distribution of secretin and secretin receptor in human cerebellum". NeuroReport 16 (3): 219–222. doi:10.1097/00001756-200502280-00003. PMID 15706223.
- Lam IP, Lee LT, Choi HS et al. (2009). "Bile acids inhibit duodenal secretin expression via orphan nuclear receptor small heterodimer partner (SHP)". Am. J. Physiol. Gastrointest. Liver Physiol. 297 (1): G90–G97. doi:10.1152/ajpgi.00094.2009. PMC 2711755. PMID 19372104.
- Yamagata T, Aradhya S, Mori M et al. (2002). "The human secretin gene: fine structure in 11p15.5 and sequence variation in patients with autism". Genomics 80 (2): 185–194. doi:10.1006/geno.2002.6814. PMID 12160732.
- Lee LT, Tan-Un KC, Chow BK (2006). "Retinoic acid-induced human secretin gene expression in neuronal cells is mediated by cyclin-dependent kinase 1". Ann. N. Y. Acad. Sci. 1070: 393–398. doi:10.1196/annals.1317.051. PMID 16888198.
- Onori P, Wise C, Gaudio E et al. (2010). "Secretin inhibits cholangiocarcinoma growth via dysregulation of the cAMP-dependent signaling mechanisms of secretin receptor". Int. J. Cancer 127 (1): NA–NA. doi:10.1002/ijc.25028. PMID 19904746.
- Lee LT, Tan-Un KC, Pang RT et al. (2004). "Regulation of the human secretin gene is controlled by the combined effects of CpG methylation, Sp1/Sp3 ratio, and the E-box element". Mol. Endocrinol. 18 (7): 1740–1755. doi:10.1210/me.2003-0461. PMID 15118068.
- Lu Y, Owyang C (2009). "Secretin-induced gastric relaxation is mediated by vasoactive intestinal polypeptide and prostaglandin pathways". Neurogastroenterol. Motil. 21 (7): 754–e47. doi:10.1111/j.1365-2982.2009.01271.x. PMC 2743409. PMID 19239625.
- Gandhi S, Rubinstein I, Tsueshita T, Onyuksel H (2002). "Secretin self-assembles and interacts spontaneously with phospholipids in vitro". Peptides 23 (1): 201–204. doi:10.1016/S0196-9781(01)00596-4. PMID 11814635.
- Love JW (2008). "Peptic ulceration may be a hormonal deficiency disease". Med. Hypotheses 70 (6): 1103–1107. doi:10.1016/j.mehy.2007.12.011. PMID 18280672.
- Lam IP, Lee LT, Choi HS, Chow BK (2006). "Localization of small heterodimer partner (SHP) and secretin in mouse duodenal cells". Ann. N. Y. Acad. Sci. 1070: 371–375. doi:10.1196/annals.1317.047. PMID 16888194.
- Luttrell LM (2008). "Reviews in molecular biology and biotechnology: transmembrane signaling by G protein-coupled receptors". Mol. Biotechnol. 39 (3): 239–264. doi:10.1007/s12033-008-9031-1. PMID 18240029.
- Du K, Couvineau A, Rouyer-Fessard C et al. (2002). "Human VPAC1 receptor selectivity filter. Identification of a critical domain for restricting secretin binding". J. Biol. Chem. 277 (40): 37016–37022. doi:10.1074/jbc.M203049200. PMID 12133828.
- Portela-Gomes GM, Johansson H, Olding L, Grimelius L (1999). "Co-localization of neuroendocrine hormones in the human fetal pancreas". Eur. J. Endocrinol. 141 (5): 526–533. doi:10.1530/eje.0.1410526. PMID 10576771.
- Mutoh H, Ratineau C, Ray S, Leiter AB (2000). "Review article: transcriptional events controlling the terminal differentiation of intestinal endocrine cells". Aliment. Pharmacol. Ther. 14 Suppl 1: 170–5. PMID 10807420.
- Overview at colostate.edu
- Secretin at the US National Library of Medicine Medical Subject Headings (MeSH)
- Physiology at MCG 6/6ch2/s6ch2_17