GH RESPONSES TO INTRAVENOUS BOLUS INFUSIONS OF GH-RELEASING HORMONE AND GH-RELEASING PEPTIDE-2 SEPARATELY AND IN COMBINATION IN ADULT VOLUNTEERS

OBJECTIVE Synthetic growth hormone releasing peptides (GHRP) have pote nt GH-releasing activity in vivo and in vitro. The nature of the inter action of GHRP and naturally occurring GH releasing hormone (GHRH) is still far from clear. We investigated GH release On response to indivi dual peptide doses or combined doses of GHRH1-29NH(2) and GHRP-2, a no vel GH-releasing peptide, in normal adults. DESIGN Subjects underwent three tests in a randomized order: (1) i.v. bolus of GHRH1-29NH(2) (1 mu g/kg BW), (2) i.v. bolus of GHRP-5 (1 mu g/kg BW), (3) i.v, bolus o f GHRH1-29NH(2) combined with GHRP-5 (same dosages). SUBJECTS Eight he althy non-obese male volunteers, aged 25-34 years. MEASUREMENTS Serum GH concentrations were measured by IRMA at -15, 0, +10, 20, 30, 45, 60 , 75, 90 and 120 minutes after the boluses. RESULTS Peak GH levels in response to GHRH1-29NH(2), GHRP-5 and the combined GHRH1-29NH(2) and G HRP-2 administrations were observed between 20 and 45 minutes. Peak GH levels at 30 minutes were 32.8 +/- 27.3 (mean +/- SD), 109.7 +/- 56.1 and 140.9 +/- 80.6 mU/l, respectively. The area under the curve for G H levels (GH AUG) calculated for the first 90 minutes after the GHRH1- 29NH(2) test (2061.2 +/- 1601.9 mU/lmin) was significantly lower than those after GHRP-5 (6205>1 +/- 3216.9mU/lmin) and the combined GHRH1-2 9NH(2) and GHRP-5 challenge (9788.3 +/- 5530.4mU/lmin) (P=0.0003 and P =0.00005, Methods respectively; paired Student's t-test for log transf ormed data). Although the GH AUC of the GHRP-2 test and the combined G HRH1-29NH(2) and GHRP-2 test differed significantly (P = 0.016, t-test ), the latter was not significantly different from the sum of the GH A UCs of each subject after the separate test. CONCLUSION Although the G H releasing potency of GHRP-2 significantly exceeded that of GHRH1-29N H(2), we were not able to demonstrate synergy between the two substanc es. It is possible that GHRP-2 given in our study in higher molar quan tities than GHRH1-29NH(2) masked the effect of the latter.