Opiate suppression of LH secretion involves central receptors different from those mediating opiate effects on prolactin secretion.

The involvement of mu- and kappa-opiate receptors in the regulation of LH and prolactin secretion was investigated in long-term ovariectomized rats using selective opiate receptor agonists and antagonists. The mu-agonists morphine and [D-Ala2,MePhe4,Gly5-ol]-enkephalin (DAGO) suppressed LH levels in a dose-related manner. The benzomorphane (-)-5,9-dimethyl-2'-hydroxy-2-(tetrahydrofurfuryl)-6,7-benzomorphan tartrate (MR 2034; a designated kappa-agonist) also suppressed LH levels, whereas another benzomorphane kappa-agonist (-)-5,9-dimethyl-2'-hydroxy-2-(2-methoxy-propyl)-6,7-benzomorphan hydrobromide (MRZ 2549) had no effect on the levels of this hormone. Pretreatment with the highly selective mu-antagonist beta-funaltrexamine (beta-FNA), the fumarate methyl ester derivative of naltrexone, blocked the actions of both mu-agonists and MR 2034, indicating that opiate suppression of LH secretion is mediated by mu-receptors. This was further confirmed by in-vitro studies: the KCl-induced release of LHRH from perifused hypothalami obtained from ovariectomized rats was significantly reduced by DAGO but not by MRZ 2549. Prolactin secretion was stimulated in a dose-dependent manner by both mu- and kappa-agonists. The stimulation caused by morphine and DAGO was antagonized by beta-FNA, whereas that caused by the kappa-agonists MR 2034 and MZR 2549 was resistant to blockade by beta-FNA but not by naloxone (an antagonist which blocks all classes of opiate receptors when given in high doses). Thus prolactin secretion seems to be regulated by both mu- and kappa-opiate receptors, whereas the effects on LH secretion seem to involve mu-receptors only.