Different effects of growth hormone releasing peptide (GHRP-6) and GH-releasing hormone on GH release in endogenous and exogenous hypercortisolism

Abstract

OBJECTIVE Chronic hypercortisolism is associated with decreased OH responsiveness to GHRH, GHRP-6 is a synthetic hexapeptide that releases GH in several species, including man, As GHRH and GHRP-6 apparently stimulate GH release by different mechanisms, we evaluated the ON responses to these peptides in patients with endogenous and exogenous glucocorticoid excess and also in control subjects.DESIGN Six patients with endogenous hypercortisolism, nine with exogenous glucocorticoid excess; and 10 normal controls were submitted to three tests, in random order, with GHRH (100 mu g), GHRP-6 (1 mu g/kg) or GHRP+GHRP-6, in the same doses, i.v., on separate days.MEASUREMENTS GH was measured by immunofluorometric assay, IGF-I was determined by radio immunoassay, Plasma glucose was measured by the glucose-oxidase technique.RESULTS Peak GH values (mean+/-SE; mu g/l) after GHRH were significantly blunted in endogenous (2.0 +/- 0.7) and exogenous (3.6 +/- 1.2) hypercortisolae mic patients compared to controls (24.9 +/- 5.1), the endogenous group had lower peak GH values after GHRP-6 alone (7.7 +/- 1.9) or together with GHRH (18.8 +/- 5.8) than those observed in controls (GHRP-6: 22.1 +/- 3.6; GHRH+GHRP-6: 77.4 +/- 15.0) and in exogenous hypercortisolism (27.4 +/- 6.2 and 78.1 +/- 19.9). There were no differences in the GH responses to GHRP-6 alone or in combination with GHRH when controls were compared to the exogenous group, No changes in plasma IGF-I and glucose levels were observed.CONCLUSIONS Our results suggest that hypercortisolism had a different effect on the ON-releasing mechanisms stimulated by GHRH and GHRP-6. Moreover, in endogenous hypercortisolism both GHRN and GHRP-6 pathways are affected, while in the exogenous group GHRP-6 releasing mechanisms are apparently preserved.