ABSTRACT
The initial growth hormone-releasing peptide (GHRP), Tyr-n-Trp-Gly-PheMet-NH2 was developed in 1976 (1), and since then the GHRPs have been greatly expanded at many different levels including accomplishments of both potentially practical and theoretical value. There are now three major chemical classes of GHRP (i.e., peptides, partial peptides, and nonpeptides or peptidomimetics; 2,3). Peptide GHRPs, which consist of four major types, were established between 1977 and 1980. Despite the broad range of chemistry among the GHRPs (2-12), almost all of them appear to act on the same receptor and activate the same intracellular signal transduction pathway (13,14). By 1984, the biological action of GHRP was considered sufficiently and significantly different from native GH-releasing hormone (GHRH) to propose that it may reflect the activity of a new hypothalamic hypophysiotropic hormone (15). The activity of GHRP in multiple animal species (15) and, subsequently, in humans in 1990, again strongly supported this hypothesis (16). In 1996, the seminal achievement of cloning the GHRPGH secretagogue receptor was accomplished (17). It is a new seven-transmembrane domain G-protein-coupled receptor (18). Genomic analysis supports the presence of a single highly conserved gene in human, chimpanzee, swine, bovine, rat, and mouse genomic DNA. Two immediate objectives of primary importance include isolation of the putative native GHRP-like
2 Bowers
hormone and further elucidation of how GHRP releases GH. The more longterm primary objectives are the following: (1) to determine what role a putative GHRP system might have in the physiological regulation of GH secretion; (2) to determine whether the putative GHRP-like hormone might play a role in the pathophysiological secretion of GH; and (3) to determine the possible diagnostic and therapeutic value of GHRP in various disorders of GH secretion in humans.
