Growth hormone-releasing hormone (GHRH) and pituitary adenylate cyclase-activating polypeptide (PACAP) belong to the same superfamily of regulatory neuropeptides which also comprises VIP, glucagon, secretin and GIP. Both GHRH and PACAP have been characterized on the basis of their hypophysiotropic activities. In the course of vertebrate evolution, the primary structure of GHRH has markedly diverged while the sequence of PACAP has been remarkably well preserved. In mammals, GHRH and PACAP are encoded by two distinct genes: the GHRH precursor encompases GHRH and a C-terminal-flanking peptide termed C-peptide while the PACAP precursor encompasses an N-terminal-flanking peptide termed PACAP-related peptide (PRP) and PACAP. In contrast, in all submammalian vertebrates investigated so far, and in protochordates, a GHRH-like peptide and PACAP are generated from a single precursor. In mammals, GHRH-containing neurons are confined to the infundibular and dorso-medial nuclei of the hypothalamus while PACAP-producing neurons are widely distributed in hypothalamic and extrahypothalamic areas. In fish, both GHRH- and PACAP-immunoreactive neurons are restricted to the diencephalon and directly innervate the adenohypophysis. In mammals and birds, GHRH plays a prominant role in the regulation of GH secretion. In amphibians, both GHRH and PACAP strongly activate GH release. In fish, PACAP is a potent stimulator of GH release whereas GHRH has little or no effect on GH secretion. It thus appears that GHRH and PACAP provide a very interesting model in which to study the structural and functional facets of the evolution of hypophysiotropic neuropeptides. Supported by an INSERM-JSPS exchange program and the Conseil Regional de Haute-Normandie.
03 - 04 Dec 2001
Society for Endocrinology