HEXARELIN, A NOVEL GHRP-6 ANALOG, COUNTERACTS THE INHIBITORY EFFECT OF HYDROCORTISONE ON GROWTH-HORMONE SECRETION IN ACROMEGALY

Hexarelin ( His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) is a GHRP-6 anal og with the substitution of D-tryptophan with its 2-methyl derivative. The aim of our study was to ascertain whether hexarelin was able to c ounteract the glucocorticoid-mediated increase in hypothalamic somatos tatin tone and consequent inhibition on serum GH levels in acromegalic patients. Ten patients (5 males, 5 females; age range 27-71 years; BM I range 23.3-35 kg/m(2)) with active acromegaly underwent: 1) hydrocor tisone alone: a bolus iv injection of 100 mg hydrocortisone succinate in 2 mt saline, at time -60 followed by a 120 min iv infusion of 250 m g hydrocortisone succinate in 250 mt saline, from -60 to 60 min; 2) he xarelin+hydrocortisone: a bolus iv injection of hexarelin 100 mu g, 60 min after initiation of a 2-hour hydrocortisone infusion; 3) hexareli n alone: a bolus iv injection of hexarelin at time 0, 60 min after ini tiation of a 2-hour saline infusion. The mean GH peak, expressed as pe rcent change with respect to baseline level (mean of -75 and -60 minut e samples), after hexarelin (1750+/-1157%) did not differ significantl y with respect to that observed after hexarelin+hydrocortisone (1120+/ -770%). After hydrocortisone alone the patients showed a mean decrease in GH levels as compared to baseline levels, of 47+/-7%. Our data sho w that the GH response to hexarelin in acromegaly is resistant to the inhibitor action of an acute and sustained elevation of serum cortisol levels. That hexarelin counteracts the glucocorticoid-mediated inhibi tion of GH secretion supports the hypothesis of an hexarelin-induced d ecrease in endogenous somatostatin tone.