secretin

secretin. It is a peptide hormone produced by S cells located in the duodenum of the small intestine. This hormone plays a critical role in regulating the pH of the duodenal contents by stimulating the secretion of bicarbonate-rich fluid from the pancreas and liver. The discovery of secretin in 1902 by William Bayliss and Ernest Starling at University College London marked the birth of the concept of hormones and the field of endocrinology.

Structure and synthesis

Secretin is a linear polypeptide composed of 27 amino acids, sharing structural homology with other peptides such as glucagon, vasoactive intestinal peptide, and gastric inhibitory polypeptide. The gene responsible for its production is located on chromosome 11 in humans. Synthesis begins with the translation of a preprohormone in the S cells, which is subsequently cleaved to yield the active hormone. The three-dimensional structure of secretin is stabilized by several disulfide bonds, which are crucial for its biological activity and interaction with the secretin receptor. Research into its molecular conformation has been advanced by studies at institutions like the MRC Laboratory of Molecular Biology.

Function and mechanism

The primary physiological role of secretin is to neutralize acidic chyme entering the duodenum from the stomach. When luminal pH falls below 4.5, S cells release secretin into the bloodstream. The hormone then binds to specific G protein-coupled receptors located on the basolateral membrane of ductal cells in the pancreas and bile ducts of the liver. This binding activates adenylyl cyclase, increasing intracellular cyclic AMP levels, which in turn stimulates the secretion of a watery, bicarbonate-rich solution. This process is essential for creating an optimal environment for the activity of pancreatic enzymes like trypsin and lipase, and for protecting the intestinal mucosa.

Clinical significance

Abnormalities in secretin function or secretion are implicated in several gastrointestinal disorders. In conditions such as Zollinger-Ellison syndrome, excessive gastric acid can lead to an exaggerated secretin response. Conversely, impaired secretin release may contribute to the pathophysiology of certain forms of pancreatitis. The secretin stimulation test is a diagnostic procedure historically used to assess pancreatic exocrine function, particularly in cases of cystic fibrosis or suspected pancreatic cancer. Furthermore, research has explored potential links between secretin and autism spectrum disorders, though clinical trials have not yielded consistent therapeutic benefits.

History and discovery

The discovery of secretin was a landmark event in physiology. In 1902, William Bayliss and Ernest Starling conducted experiments on dogs at University College London, demonstrating that an extract from the duodenal mucosa could stimulate pancreatic secretion even after severing all nervous connections. They coined the term "hormone" from the Greek language to describe this chemical messenger. This work directly challenged the prevailing Pavlovian theory of nervous control and established the foundation for the field of endocrinology. Their findings were first presented to the Royal Society and published in The Journal of Physiology.

Research and therapeutic uses

Ongoing research investigates the potential therapeutic applications of synthetic secretin. While its use in autism has been largely discontinued, studies explore its role in diagnosing gastrinoma and in imaging the pancreas and bile ducts during procedures like endoscopic retrograde cholangiopancreatography. Investigations into secretin receptor agonists and antagonists are being pursued for conditions like heart failure and portal hypertension, with research conducted at centers like the National Institutes of Health and the Mayo Clinic. Furthermore, its role in regulating water homeostasis in the kidney and brain remains an active area of scientific inquiry.