Hexarelin-induced growth hormone, cortisol, and prolactin release: a dose-response study.
Dose-response data for GH-releasing peptides are limited. We studied the effects of varying doses (0-1.0 microgram/kg) of hexarelin, a novel GH-releasing peptide, administered iv to healthy adult males on GH, PRL, and cortisol release. In addition, we studied the effect of administration of a single dose of GHRH-(1-29)-NH2 (1.0 microgram/kg), alone or in combination with a low dose of hexarelin (0.125 microgram/kg). Dose-response curves for the maximum GH response and maximum percent change in serum PRL and cortisol concentrations from baseline were constructed. The GH dose-response curve reached a plateau of 140 mU/L, corresponding to a hexarelin dose of 1.0 microgram/kg, with an ED50 of 0.48 +/- 0.02 microgram/kg (mean +/- SEM). The PRL dose-response curve reached a plateau of 180% for the maximum percent rise from baseline, corresponding to a hexarelin dose of 1.0 microgram/kg, with an ED50 of 0.39 +/- 0.02 microgram/kg. The cortisol dose-response curve showed a step increase to approximately 40% at a hexarelin dose of 0.5 microgram/kg. The coadministration of GHRH-(1-29)-NH2 (1.0 microgram/kg) and low dose hexarelin (0.125 microgram/kg) resulted in massive GH release (115 +/- 32.8 mU/L), a moderate rise in serum PRL (84.9 +/- 27.5%), and no rise in serum cortisol. These data show that iv hexarelin was capable of inducing GH, PRL, and cortisol release in a dose-dependent manner. Low dose hexarelin was synergistic with GHRH and potent for GH release with a minimal effect on other hormones.
Massoud
A F
AF
London Center for Pediatric Endocrinology and Metabolism, Middlesex Hospital, London, United Kingdom.
Hindmarsh
P C
PC
Brook
C G
CG
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D011388:Prolactin / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood
D001786:Blood Glucose; D006133:Growth Substances; D007328:Insulin; D009842:Oligopeptides; C086184:hexarelin; D011388:Prolactin; D013972:Thyrotropin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D006854:Hydrocortisone