The overall development of the growth hormone releasing peptide (GHRP) story has been long, unexpected, and exciting. The first unnatural pentapeptide GHRPs appeared in 1976. The combination of GHRP and growth hormone–releasing hormone was found to synergistically release growth hormone (GH) in rats in 1984, indicating the peptides’ complementary and independent actions. At this time, GHRP was hypothesized to reflect the activity of a new hypothalamic hormone. By 1989, the GHRP GH release in humans was notable and by 1996, the GHRP–growth hormone secretagogue receptor was cloned. Results of the unnatural GHRPs obtained by many talented investigators worldwide supported the possibility of a natural GHRP hormone. At last, in the December 9, 1999 issue of Nature, the probable natural GHRP hormone, ghrelin, was reported. The isolation and sequence was accomplished by the outstanding achievements of Kojima and coworkers. The chemistry and the major anatomical site of origin indeed are novel, since it is a Ser3-octanoylated 28 amino acid peptide that surprisingly appears to originate primarily in the stomach but also is present in the ventral lateral border of the hypothalamic arcuate nucleus. Without octanoylation, the peptide has no GH-releasing activity. It would be unexpected that the actions of ghrelin on GH regulation and its interactions with GH-releasing hormone and somatostatin are not the same as those obtained with the unnatural GHRPs.
Tulane Medical School, New Orleans, Louisiana, USA.
Correspondence to C.Y. Bowers, MD, Tulane Medical School, 1430 Tulane Avenue, New Orleans, LA 70112, USA; e-mail: email@example.com