Effect of GHRP-6 and GHRH on GH secretion in rats following chronic glucocorticoid treatment

The aim of our study was to investigate the effects of His-DTrp-Ala-Trp-Phe-Lys-NH2 (GHRP-6) on baseline and growth hormone-releasing hormone (GHRH) stimulated growth hormone (GH) release in conscious, freely-moving rats receiving chronic glucocorticoid treatment. Animals were treated daily for seven days with either vehicle or dexamethasone (dex, 40 micrograms/day). On the day of experimentation, rats received an i.v. injection of saline or GHRP-6 followed 15 min later by an i.v. injection of saline or rat GHRH. Three doses of GHRP-6 were evaluated, 1 microgram, 4 micrograms and 25 micrograms/kg; one dose of GHRH was evaluated, 500 ng/kg. GHRP-6 increased plasma GH levels over baseline concentrations in a dose-dependent fashion both in vehicle- and dex-treated rats. The GH response to GHRP-6 and GHRH was significantly less in dex-treated rats as compared to vehicle-treated rats. The combined administration of GHRP-6 and GHRH did not result in any change in plasma GH levels which could not be predicted from the administration of either peptide alone. Our results show that GHRP-6 is able to stimulate GH secretion in glucocorticoid-treated rats but it is unable to counteract the glucocorticoid-induced inhibition of GH secretion.