MU-OPIOID AGONISTS STIMULATE GROWTH-HORMONE SECRETION IN IMMATURE RATS

The purpose of the present study was to evaluate the opioid receptor s ubtype mediating opioid modulation of growth hormone (GH) secretion du ring ontogeny. The mu-agonist morphine and the kappa agonist U50,488 c aused a stimulation and inhibition of GH secretion, respectively, on p ostnatal 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 substan tial mu-stimulation was not observed until postnatal day 10. Intracere broventricular (i.c.v.) administration of the mu-selective peptide [D- Ala(2)-NMe-Phe(4)-Gly-ol]-enkephalin (DAMGO) elicited a marked rise in GH secretion, while administration of the delta-agonists [D-pen(2)D-p en(5)]-enkephalin (DPDPE) or deltorphin II caused only a minor and non -dose-related rise in GH secretion in neonatal rats. The relative impo rtance of mu- and delta-receptors in stimulating GH secretion was also studied in older pups (day 20). i.c.v. administration of DAMGO stimul ated GH secretion, while neither DPDPE nor deltorphin II consistently increased GH secretion. Furthermore, peripheral administration of eith er morphine or the highly selective mu-agonist sufentanil elicited mar ked GH secretion on postnatal day 20, but only combined administration of the mu-antagonist beta-funaltrexamine (beta-FNA) and the delta-ant agonist naltrindole substantially diminished these responses. These re sults suggest that both mu- and kappa-opioid receptors are involved in the regulation of GH secretion in neonatal rats. While delta-receptor s do not play a prominent independent role in this response, they may act synergistically with mu-receptors in producing stimulation.