Secretin is a hormone that controls the secretions into the duodenum, and also separately, water homeostasis throughout the body. It is produced in the S cells of the duodenum in the crypts of Lieberkühn.^[1] Its effect is to regulate the pH of the duodenal contents via the control of gastric acid secretion and buffering with bicarbonate from the centroacinar cells of the pancreas as well as intercalated ducts. It is notable for being the first hormone to be identified.^[2] In humans, the secretin peptide is encoded by the SCT gene.^[3][4]

It has recently been discovered to play a role in osmoregulation in the hypothalamus, pituitary, and kidney.^[5][6]

  Discovery

In 1902, William Bayliss and Ernest Starling were studying how the nervous system controls the process of digestion.^[7] 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.

  Structure

Secretin is initially synthesized as a 120 amino acid precursor protein. This precursor contains an N-terminal signal peptide, spacer, secretin itself (residues 28–54), and a 72-amino acid C-terminal peptide.^[3]

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.^[8]

Secretin also has an amidated carboxyl-terminal amino acid which is valine.^[9] The sequence of amino acids in secretin is:

• H₂N–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–CONH₂.^[9]

  Physiology

  Production

Secretin is synthesized in cytoplasmic secretory granules of S-cells, which are found mainly in the mucosa of the duodenum, and in smaller numbers in the jejunum of the small intestine.^[10]

  Stimulus

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.^[11] Also, the secretion of secretin is increased by the products of protein digestion bathing the mucosa of the upper small intestine.^[12]

It is the active form of prosecretin. This 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^[13] Other factors are also involved in the release of secretin such as bile salts and fatty acids, which result in additional bicarbonates being added to the small intestine.^[14] 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.^[15]

  Function

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.^[16] 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 in order to buffer the incoming protons of the acidic chyme.^[17] It also enhances the effects of cholecystokinin to induce the secretion of digestive enzymes and bile from pancreas and gallbladder, respectively.

It counteracts blood glucose concentration spikes by triggering increased insulin release from pancreas, following oral glucose intake.^[18]

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.^[19]: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.^{[citation needed]}

In addition, secretin stimulates pepsin secretion from chief cells, which can help break down proteins in food digestion. It also stimulates release of glucagon, pancreatic polypeptide and somatostatin.^[11]

  Uses

Secretin has been widely used in medical field especially in pancreatic functioning test because it increases pancreatic secretions. Secretin is either injected^[20] or given through the tube that is inserted through nose, stomach then duodenum.^[21] This test can provide information about whether there are any abnormalities in pancreas which can be gastrinoma, pancreatitis or pancreatic cancer.

Secretin has been proposed as a possible treatment for autism based on a hypothetical gut-brain connection, but as yet there is no evidence to support it as effective.^[22]

  Osmoregulation

Secretin modulates water and electrolyte transport in pancreatic duct cells,^[23] liver cholangiocytes,^[24] and epididymis epithelial cells.^[25] It has also been recently been found to play a role in the vasopressin-independent regulation of renal water reabsorption.^[5]

Secretin is found in the hypothalamus and neurohypophysis, During increased osmolality it is released from the posterior pituitary. In the hypothalamus, it activates vasopressin release.^[6]

It has been suggested that abnormalities in such secretin release could explain the abnormalities underlying type D Syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH).^[6] In these individuals, vasopressin release and response are normal, although abnormal renal expression, translocation of aquaporin 2, or both are found.^[6] 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."^[6]

  See also

• Secretin receptor

  References

  Further reading

  External links

• Overview at colostate.edu
• Secretin at the US National Library of Medicine Medical Subject Headings (MeSH)
• Physiology at MCG 6/6ch2/s6ch2_17