title: Hexarelin, a novel GHRP-6 analog, counteracts the inhibitory effect of hydrocortisone on growth hormone secretion in acromegaly.
abstract: Hexarelin (His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) is a GHRP-6 analog with the substitution of D-tryptophan with its 2-methyl derivative. The aim of our study was to ascertain whether hexarelin was able to counteract the glucocorticoid-mediated increase in hypothalamic somatostatin tone and consequent inhibition on serum GH levels in acromegalic patients. Ten patients (5 males, 5 females; age range 27-71 years; BMI range 23.3-35 kg/m2) with active acromegaly underwent: 1) hydrocortisone alone: a bolus iv injection of 100 mg hydrocortisone succinate in 2 mL saline, at time -60 followed by a 120 min iv infusion of 250 mg hydrocortisone succinate in 250 mL saline, from -60 to 60 min; 2) hexarelin+hydrocortisone: a bolus iv injection of hexarelin 100 micrograms, 60 min after initiation of a 2-hour hydrocortisone infusion; 3) hexarelin alone: a bolus iv injection of hexarelin at time 0, 60 min after initiation of a 2-hour saline infusion. The mean GH peak, expressed as percent change with respect to baseline level (mean of -75 and -60 minute samples), after hexarelin (1750 +/- 1157%) did not differ significantly 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 show 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 inhibition of GH secretion supports the hypothesis of an hexarelin-induced decrease in endogenous somatostatin tone.
authors.affiliation: Cattedra di Clinica Medica, University of Brescia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Giustina
authors.forename: E
authors.initials: E
authors.lastname: Bresciani
authors.forename: G
authors.initials: G
authors.lastname: Bugari
authors.forename: A R
authors.initials: AR
authors.lastname: Bussi
authors.forename: R
authors.initials: R
authors.lastname: Deghenghi
authors.forename: B
authors.initials: B
authors.lastname: Imbimbo
authors.forename: G
authors.initials: G
authors.lastname: Giustina
mesh_terms: D000172:Acromegaly / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D006133:Growth Substances; D009842:Oligopeptides; C086184:hexarelin; D013006:Growth Hormone; C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone