DIFFERENT EFFECTS OF GROWTH-HORMONE RELEASING PEPTIDE (GHRP-6) AND GH-RELEASING HORMONE ON GH RELEASE IN ENDOGENOUS AND EXOGENOUS HYPERCORTISOLISM

OBJECTIVE Chronic hypercortisolism is associated with decreased OH res ponsiveness to GHRH, GHRP-6 is a synthetic hexapeptide that releases G H in several species, including man, As GHRH and GHRP-6 apparently sti mulate GH release by different mechanisms, we evaluated the ON respons es to these peptides in patients with endogenous and exogenous glucoco rticoid 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 orde r, with GHRH (100 mu g), GHRP-6 (1 mu g/kg) or GHRP+GHRP-6, in the sam e doses, i.v., on separate days. MEASUREMENTS GH was measured by immun ofluorometric assay, IGF-I was determined by radio immunoassay, Plasma glucose was measured by the glucose-oxidase technique. RESULTS Peak G H values (mean+/-SE; mu g/l) after GHRH were significantly blunted in endogenous (2.0 +/- 0.7) and exogenous (3.6 +/- 1.2) hypercortisolae m ic 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 hypercortisolis m (27.4 +/- 6.2 and 78.1 +/- 19.9). There were no differences in the G H 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 g lucose levels were observed. CONCLUSIONS Our results suggest that hype rcortisolism had a different effect on the ON-releasing mechanisms sti mulated by GHRH and GHRP-6. Moreover, in endogenous hypercortisolism b oth GHRN and GHRP-6 pathways are affected, while in the exogenous grou p GHRP-6 releasing mechanisms are apparently preserved.