SUPPRESSION OF GROWTH-HORMONE (GH) SECRETION BY A SELECTIVE GH-RELEASING HORMONE (GHRH) ANTAGONIST - DIRECT EVIDENCE FOR INVOLVEMENT OF ENDOGENOUS GHRH IN THE GENERATION OF GH PULSES

To study the potential involvement of growth hormone-releasing hormone (GHRH) in the generation of growth hormone (GH) pulses in humans we have used a competitive antagonist to the GHRH receptor, (N-Ac-Tyr1,D-Arg2)GHRH(1-29)NH2(GHRH-Ant). Six healthy young men were given a bolus injection of GHRH-Ant 400 mug/kg body wt or vehicle at 2200 h and nocturnal GH concentrations were assessed by every 10-min blood sampling until 0800 h. Integrated total and pulsatile GH secretion were suppressed during GHRH-Ant treatment by 40 +/- 6 (SE) % and 75 +/- 5%, respectively. GHRH-Ant suppressed maximum (7.6 +/- 2.2 vs 1.8 +/- 0.5 mug/liter; P < 0.001) and mean (3.3-1.0 vs 1.1 +/- 0.2 mug/liter; P = 0.02) GH pulse amplitudes. There was no change in integrated nonpulsatile GH levels, pulse frequency, or interpulse GH concentration. GHRH-Ant 400 mug/kg also suppressed the GH responses to intravenous boluses of GHRH 0.33 mug / kg given 1, 6, 12, and 24 h later by 95, 81, 59, and 4%, respectively. In five healthy men, the responses to 10-fold larger GHRH boluses (3.3 mug/kg) were suppressed by 82 and 0%, 1 and 6 h after GHRH-Ant 400 mug/kg, respectively. These studies provide the first direct evidence that endogenous GHRH participates in the generation of spontaneous GH pulses in humans.