Introduction and overview

Growth hormone (GH) releasing peptides (GHRPs) were developed by Bowers and co-workers in the early 1980s, specifically as GH secretagogues (Bowers et al., 1980; Bowers et al., 1991). These small, synthetic peptide molecules, created by modifying the structure of met-enkephalin, include the hexapeptides GHRP-6 (His-D-Tryp-Ala-Trp-D-Phe-Lys-NH2), -1, -2 and hexarelin (His-D-2–Methyl-Try-Ala- Trp-DPhe-Lys-NH2), in which the D-tryptophan has been substituted with its 2-methyl derivative. Oral administration of the GHRPs stimulates GH release but the bioavailability, and hence GH stimulatory potency, is much greater after parenteral administration; an oral GHRP-6 dose of 300 µg/kg produces a comparable increase in serum GH concentration to a 1 µg/kg intravenous (iv) bolus (Bowers et al., 1992; Hartman et al., 1992). The onset of action of GHRP is somewhat slower after oral than iv administration, however the duration of action is similar for both, averaging about 120–150 minutes (Hartman et al., 1992). The reduced potency of oral GHRP and this relatively limited duration of action prompted the search for GH secretagogues with a longer duration of action and greater oral bioavailability (see below).

Preliminary data indicate that it may be possible to administer GHRP transdermally (Fleisher et al., 1995), and intranasal administration of hexarelin has been shown to stimulate GH secretion in healthy elderly people and increase growth velocity and serum insulin-like growth factor-I (IGF-I) concentrations in short children (Laron et al., 1995). The GHRPs are well tolerated and to date few side effects have been reported. The acute stimulatory effects of GHRP-6 on GH secretion are independent of gender (Penalva et al., 1993a) and there are no reports of gender-related differences in GH responses to the other GHRPs.