Preprosecretin

Preprosecretin is the ribosomally synthesized precursor of the gastrointestinal hormone secretin. It is encoded by the SCT gene and produced mainly by enteroendocrine S cells in the duodenum and proximal small intestine.

The polypeptide contains an N-terminal signal peptide that directs the growing chain into the secretory pathway, followed by a pro-region that flanks the secretin sequence. After entry into the endoplasmic reticulum, the signal peptide is cleaved to form prosecretin. Endoproteolytic processing by prohormone convertases cleaves the prohormone at specific dibasic sites to release the mature secretin, which is a small peptide of about 27 amino acids. Post-translational modifications, including C-terminal amidation, yield the active hormone.

Secretin's primary role is to regulate the pH of intestinal contents. It binds to the secretin receptor on pancreatic ductal cells, activating a Gs-coupled pathway and increasing cyclic AMP, which stimulates bicarbonate-rich fluid secretion from the pancreas and biliary system. This bicarbonate helps neutralize chyme and optimizes digestive enzyme activity. Secretin can also influence gastric acid secretion and gut motility indirectly.

In humans, preprosecretin processing is tightly controlled to ensure timely release of active secretin in response to luminal acid. The SCT gene and its peptide products form part of the broader secretin signaling network that coordinates digestive processes.