Endocrine activities of alexamorelin (Ala-His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2), a synthetic GH secretagogue, in humans

Objective: Peptidyl and non-peptidyl synthetic GH secretagogues (GHS) posse ss significant GH-, prolactin (PRL)- and ACTH/cortisol-releasing activity a fter i.v. and even p.o. administration, acting via specific hypothalamo-pit uitary receptors in both animals and humans. The hexapeptide hexarelin (HEX ) is a paradigmatic GHS whose activities have been widely studied in humans . The heptapeptide Ala-His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2 (alexamorel in, ALEX) is a new synthetic molecule which inhibits GHS binding in vitro, but its endocrine activity has never been studied in humans. Design: In six young adults we studied the effects of 1.0 and 2.0 mu g/kg i .v. ALEX or HEX on GH, PRL, ACTH, cortisol and aldosterone levels and those of 20 mg p.o. (approximate to 300 mu g/kg) on GH levels. Results: Basal GH, PRL, ACTH, cortisol and aldosterone levels in all testin g sessions were similar. ALEX and HEX (1.0 and 2.0 mu g/kg i.v.) induced th e same dose-dependent increase of GH and PRL levels. Both ALEX and HEX indu ced a dose-dependent increase of ACTH and cortisol levels. The ACTH and cor tisol responses to the highest ALEX dose were significantly higher than tho se after HEX. Aldosterone levels significantly increased after both i.v. AL EX doses, but not after HEX. The GH response to 20 mg p.o. ALEX was higher, though not significantly, than that to the same HEX dose. Conclusion: ALEX, a new GHS, shows the same GH-releasing activity as HEX. O n the other hand, ALEX seems endowed with an ACTH-releasing activity more m arked than that of HEX; this evidence could explain the significant increas e of aldosterone levels after its i.v. administration.