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

Abstract

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 μg/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 μg/liter; P < 0.001) and mean (3.3±1.0 vs 1.1±0.2 μg/liter; P = 0.02) GH pulse amplitudes. There was no change in integrated non-pulsatile GH levels, pulse frequency, or interpulse GH concentration. GHRH-Ant 400 μg/kg also suppressed the GH responses to intravenous boluses of GHRH 0.33 μg/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 μg/kg) were suppressed by 82 and 0%, 1 and 6 h after GHRH-Ant 400 μg/kg, respectively. These studies provide the first direct evidence that endogenous GHRH participates in the generation of spontaneous GH pulses in humans.