The effect of an opiate antagonist on the hormonal changes induced by hexarelin.

Growth hormone-releasing peptides (GHRPs) stimulate growth hormone (GH) release in vitro and in vivo in animals and in humans. GHRPs were developed by modification of the structure of met-enkephalin but GHRP-6 does not activate opiod receptors in animal studies. These agents may well have diagnostic and/or long-term therapeutic potential in the future so their effects on opiod receptors need to be clarified in humans as well. Hexarelin is a recently developed six amino acid residue GHRP. We have investigated the effects of 100 micrograms/kg i.v. dose of the opiate antagonist naloxone and 2 micrograms/kg i.v. hexarelin or placebo on serum GH, prolactin, TSH, cortisol and plasma ACTH in 12 healthy volunteers in a double-blind, randomized trial. Hexarelin significantly stimulated the peak serum levels and area under the curve for circulating GH and this effect was not modulated by naloxone. Hexarelin also caused significant elevation of circulating prolactin, cortisol and ACTH but did not influence circulating TSH levels. The effect of naloxone on cortisol and ACTH was stimulatory, while it did not influence prolactin, GH and TSH levels. The effect of the two drugs together on cortisol and ACTH was less than additive. This study confirms that the activation of opiate receptors does not play a role in the GH-releasing effect of growth hormone-releasing peptides in humans.