Secretin: A potential neurosecretory factor regulating body water homeostasis.

Abstract

Secretin, originally isolated from the upper intestinal mucosal extract, is a classical gastrointestinal hormone that has recently implicated to play a neuromodulatory role in higher centers, including cerebellumand hippocampus. On the other hand, its functions in the hypothalamo-neurohypophysial axis have not fully appreciated. Using secretin receptor-null (SCTR−/−) mice, we showed previously that secretin exerts peripheral functions in the kidney, where it modulates the process of renal water reabsorption by stimulating the expression and trafficking of aquaporin-2. Now, we provide evidence to show the activity of secretin at the hypothalamo-pituitary level to regulate body water homeostasis by demonstrating (1) the presence of secretin and its receptor in the hypothalamo-neurohypophysial axis; (2) secretin-induced activation of cfos and vasopressin (Vp) expression in the magnocellular neurons within Paraventricular (PVN) and Supraoptic Nuclei (SON); (3) the in vitro and in vivo stimulatory effects of secretin on Vp secretion; (4) augmentations of secretin and its receptor expression in the hypothalamus and pituitary under water deprivation; (5) TTX- and Cd2+-dependent release of secretin from the posterior pituitary during plasma hyperosmolality; and (6) electrical stimulation of SON and PVN led to a pulsatile release of secretin in peripheral circulation measured in the jugular vein. Taken together, these results revealed that secretin is a novel neurosecretory hormone from the neurohypophysis to modulate body fluid and electrolyte homeostasis.