Growth Hormone (GH)-Releasing Peptide-6 Requires Endogenous Hypothalamic GH-Releasing Hormone for Maximal GH Stimulation

GH-releasing peptide-6 (GHRP-6) is a potent GH secretagogue that releases GH by uncertain mechanisms. To assess whether GHRH is required for GH release by GHRP-6 in humans, we used the specific antagonist to GHRH (N-Ac-Tyr¹,d-Arg²)GHRH(1–29)NH₂ (GHRH Ant). We have previously shown that GHRH-Ant (400 μg/kg) blocked the GH response to 0.33 and 3.3 μg/kg boluses of GHRH by 95% and 81%, respectively. Nine healthy men between the ages of 20 and 30 yr were studied on two occasions. They received either saline or GHRH-Ant (400 μg/kg, iv) at 0840 h, followed by GHRP-6 (1μ g/kg, iv bolus) at 0900 h. Blood was sampled every 10 min from 0800–1100 h. GH responses were measured as the maximal increase over the baseline GH concentration and as the area under the curve. GHRH-Ant eliminated most of the GH response to GHRP-6 [maximal increase over the baseline GH concentration, 33.8 ± 4.8 vs. 6.2 ± 1.8 μg/L (mean ±sem; P< 0.0001); area under the curve, 1701 ± 278 vs. 376 ± 113 μg/min·L (P < 0.001)]. These data show that endogenous GHRH is necessary for most of the GH response to GHRP-6 in humans.