Growth hormone (GH) responses to the hexapeptide GH-releasing peptide and GH-releasing hormone (GHRH) in the cynomolgus macaque: evidence for non-GHRH-mediated responses.

GH-releasing peptide (GHRP; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2), a hexapeptide derived from enkephalin, has been shown to have GH-releasing activity in man and several animal species. To characterize the GHRP dose-response curve and compare it with that of GH-releasing hormone [GHRH-(1-44)NH2], six unanesthetized young adult cynomolgus macaques were tested with a range of iv doses of GHRP or GHRH in random order. Animals were fitted with vests and tethers. Blood samples were obtained before and at 15-min intervals after the administration of drugs. Doses ranged from 0.03-3 mg/kg for GHRP and from 1-30 micrograms/kg for GHRH. The dose-response curves for the two peptides were not parallel. GHRP had lower potency, but evoked a much higher peak GH response than GHRH (greater than 55 vs. 12 micrograms/L). Because one of the proposed mechanisms of action of GHRP is the inhibition of somatostatin (SS), we tested the effects of propranolol, which inhibits SS, on the GH responses to GHRH and GHRP. Propranolol was given at a dose of 14 micrograms/kg, iv, 10 min before the injection of saline, GHRH (10 micrograms/kg), or GHRP (1 mg/kg). GH responses to propranolol alone did not differ from those to placebo (peak, 6 +/- 2 vs. 8 +/- 2 micrograms/L). However, propranolol pretreatment doubled the GH responses to both GHRH and GHRP compared with those to GHRH or GHRP alone 28 +/- 5 micrograms/L vs. 14 +/- 5 (P less than 0.05) and 54 +/- 2 vs. 25 +/- 6 micrograms/L (P less than 0.001), respectively]. These results show that GHRP causes a potent dose-dependent release of GH in this primate species. Since GHRP can produce a greater maximal GH response than GHRH, mechanisms other than release of endogenous GHRH must be involved.