Growth Hormone (GH)-Releasing Peptide Stimulates GH Release in Normal Men and Acts Synergistically with GH-Releasing Hormone*

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Abstract
The acute GH release stimulated by the synthetic hexapeptide, His-D Trp-Ala-Trp-DPhe-Lys-NH2 [GH releasing peptide (GHRP)], was determined in 18 normal men and compared with the effects of GH-releasing hormone, GHRH-(1-44)-NH2. Specificity of effect was assessed by measurement of serum PRL, LH, TSH, and cortisol. GHRP was administered at doses of 0.1, 0.3, and 1.0 .mu.g/kg by iv bolus. GHRH at a dose of 1.0 .mu.g/kg was administered alone and together with various does of GHRP. No adverse clinical effects or laboratory abnormalities were observed in response to GHRP. A side-effect of mild facial flushing of 1- to 3-min duration occurred in 16 of the 18 subjects who received GHRH-(1-44)-NH2. Mean (.+-.SEM) peak serum GH levels after injection of placebo and 0.1, 0.3, and 1.0 .mu.g/kg GHRP were 1.2 .+-. 0.3, 7.6 .+-. 2.5, 16.5 .+-. 4.1, and 68.7 .+-. 15.5 .mu.g/L, respectively. The submaximal dosages of 0.1 and 0.3 .mu.g/kg GHRP plus 1 .mu.g/kg GHRH stimulated GH release synergistically. Serum PRL and cortisol levels rose about 2-fold above basal levels only at the 1 .mu.g/kg dose of GHRP, and there were no changes in serum LH and TSH over the first hour after administration of the peptide(s). GHRP is a potent secretagogue of GH in normal men. Since GHRP and GHRH together stimulate GH release synergistically, these results suggest that GHRP and GHRH act independently. This supports our hypothesis that the GH-releasing activity of GHRP reflects a new physiological system in need of further characterization in animals and man.