Secretin, glucagon, gastric inhibitory polypeptide, parathyroid hormone, and related peptides in the regulation of the hypothalamus-pituitary-adrenalaxis

Secretin. glucagon, gastric inhibitory polypeptide (GIP), and parathyroid h ormone (PTH) belong, together with vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase (AC)-activating polypeptide, to a Family of pep tides (the VIP-secretin-glucagon family), which also includes growth hormon e-releasing hormone and exendins. All the members of this peptide family po ssess a remarkable amino-acid sequence homology, and bind to G-protein-coup led receptors, whose signaling mechanism primarily involves AC/protein kina se A and phospholipase C/protein kinase C cascades. VIP and pituitary AC-ac tivating polypeptide play a role in the regulation of the hypothalamus-pitu itary-adrenal (HPA) axis, and in this: review we survey findings that also other members of the VIP-secretin-glucagon Family may have the same functio n. Secretin and secretin receptors are expressed in the hypothalamus and pi tuitary gland, and secretin inhibits adrenocorticotropic hormone (ACTH) rel ease. No evidence is available for the presence of secretin receptors in ad renal glands, but secretin selectively depresses the glucocorticoid respons e to ACTH of dispersed zona fasciculata-reticularis (ZF/R) cells. Glucagon and glucagon-like peptide-1 are contained in the hypothalamus, and all the components of the HPA axis are provided with glucagon and glucagons-like-1 receptors. These peptides exert a short-term inhibitory effect on stress-in duced pituitary ACTH release and depress the ZF/R cell response to ACTH by inhibiting the AC/protein kinase A cascade; they also stimulate hypothalami c arginine-vasopressin release. GIP receptors are present in the ZF/R of th e normal adrenals, and are particularly abundant in some types of adrenocor tical adenomas and hyperplasias. GIP, through the activation of the AC/prot ein kinase A cascade, evokes a sizeable glucocorticoid secretagogue effect, leading to the identification of a food/GIP-dependent Gushing's syndrome. PTH and PTH-related protein are expressed in the hypothalamus and pituitary gland, and PTH and PTH-related protein receptors in all the components of the HPA axis. Both peptides enhance ACTH and arginine-vasopressin release, as well as stimulate aldosterone and glucocorticoid secretion of dispersed zona glomerulosa and ZF/R cells, respectively. The involvement of growth ho rmone-releasing hormone and exendins in the functional regulation of the HP A axis has not yet been extensively investigated. (C) 2000 Elsevier Science Inc. All rights reserved.