GH responses to intravenous bolus infusions of GH releasing hormone and GH releasing peptide 2 separately and in combination in adult volunteers

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Abstract
Synthetic growth hormone releasing peptides (GHRP) have potent GH-releasing activity in vivo and in vitro. The nature of the interaction of GHRP and naturally occurring GH releasing hormone (GHRH) is still far from clear. We investigated GH release in response to individual peptide doses or combined doses of GHRH1-29NH2 and GHRP-2, a novel GH-releasing peptide, in normal adults. Subjects underwent three tests in a randomized order: (1) i.v. bolus of GHRH1-29NH2 (1 microgram/kg BW), (2) i.v. bolus of GHRP-2 (1 microgram/kg BW), (3) i.v. bolus of GHRH1-29NH2 combined with GHRP-2 (same dosages). Eight healthy non-obese male volunteers, aged 25-34 years. Serum GH concentrations were measured by IRMA at -15, 0, +10, 20, 30, 45, 60, 75, 90 and 120 minutes after the boluses. Peak GH levels in response to GHRH1-29NH2, GHRP-2 and the combined GHRH1-29NH2 and GHRP-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 GH levels (GH AUC) calculated for the first 90 minutes after the GHRH1-29NH2 test (2061.2 +/- 1601.9 mU/lmin) was significantly lower than those after GHRP-2 (6205.1 +/- 3216.9 mU/lmin) and the combined GHRH1-29NH2 and GHRP-2 challenge (9788.3 +/- 5530.4 mU/lmin) (P = 0.0003 and P = 0.00005, respectively; paired Student's t-test for log transformed data). Although the GH AUC of the GHRP-2 test and the combined GHRH1-29NH2 and GHRP-2 test differed significantly (P = 0.016, t-test), the latter was not significantly different from the sum of the GH AUCs of each subject after the separate tests. Although the GH releasing potency of GHRP-2 significantly exceeded that of GHRH1-29NH2, we were not able to demonstrate synergy between the two substances. It is possible that GHRP-2 given in our study GHRP-2 significantly exceeded that of GHRH1-29NH2, we were not able to demonstrate synergy between the two substances. It is possible that GHRP-2 given in our study in higher molar quantities than GHRH1-29NH2 masked the effect of the latter.