mu-Opioid agonists stimulate growth hormone secretion in immature rats

The purpose of the present study was to evaluate the opioid receptor subtype mediating opioid modulation of growth hormone (GH) secretion during ontogeny. The mu-agonist morphine and the kappa agonist U50,488 caused a stimulation and inhibition of GH secretion, respectively, on postnatal day 10. Studies on postnatal days 2, 5, 10, 15 and 20 showed that kappa-inhibition could be observed as early as day 2, but substantial mu-stimulation was not observed until postnatal day 10. Intracerebroventricular (i.c.v.) administration of the mu-selective peptide [D-Ala2-NMe-Phe4-Gly-ol]-enkephalin (DAMGO) elicited a marked rise in GH secretion, while administration of the delta-agonists [D-pen2D-pen5]-enkephalin (DPDPE) or deltorphin II caused only a minor and non-dose-related rise in GH secretion in neonatal rats. The relative importance of mu- and delta-receptors in stimulating GH secretion was also studied in older pups (day 20). i.c.v. administration of DAMGO stimulated GH secretion, while neither DPDPE nor deltorphin II consistently increased GH secretion. Furthermore, peripheral administration of either morphine or the highly selective mu-agonist sufentanil elicited marked GH secretion on postnatal day 20, but only combined administration of the mu-antagonist beta-funaltrexamine (beta-FNA) and the delta-antagonist naltrindole substantially diminished these responses. These results suggest that both mu- and kappa-opioid receptors are involved in the regulation of GH secretion in neonatal rats. While delta-receptors do not play a prominent independent role in this response, they may act synergistically with mu-receptors in producing stimulation.