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Growth Hormone (GH)-Releasing Peptide-6 Requires Endogenous Hypothalamic GH-Releasing Hormone for Maximal GH Stimulation¹

Departments of Internal Medicine, University of Michigan and Ann Arbor Veterans Affairs Medical Center, Ann Arbor, Michigan 48109; and the Department of Medicine, Tulane University (C.Y.B.), New Orleans, Louisiana 70112

Address all correspondence and requests for reprints to: Craig A. Jaffe, M.D., Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan Medical Center, 3920 Taubman, Ann Arbor, Michigan 48109-0354. E-mail: cjaffe{at}umich.edu

Abstract

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 (1 µg/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.

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