Endogenous opioid peptide modulation of LH secretion in the ewe lamb: possible involvement of 5-hydroxytryptamine

Abstract

ABSTRACT Evidence from several species suggests that the endogenous opioid peptides participate in the regulation of gonadotrophin and prolactin secretion. The aim of the present study involving intact and ovariectomized prepubertal ewe lambs was to compare the effects in vivo of an opioid peptide agonist d-Ala2,N-Phe4,Met(0)ol5]-enkephalin (FK 33–824) and antagonist, naloxone, on concentrations of LH and prolactin in plasma, and levels of neurotransmitter metabolites in cerebrospinal fluid (CSF), with their effects in vitro on the release of gonadotrophin-releasing hormone (GnRH) and neurotransmitters from isolated median eminences. Infusion of FK 33–824 (0·5 mg/30 min) in vivo depressed plasma LH levels in both intact and ovariectomized lambs; this effect could be reversed by naloxone. In ovariectomized lambs, the inhibitory action of FK 33–824 on plasma LH levels was associated with a 13% rise in the concentration of the metabolite of 5-hydroxytryptamine, 5-hydroxyindolacetic acid (5-HIAA). Concurrent administration of naloxone resulted in an abrupt 33% fall in CSF levels of 5-HIAA. No significant changes in plasma concentrations of prolactin or CSF concentrations of the metabolites of dopamine were observed in response to the administration of FK 33–824 or FK 33–824 plus naloxone. That FK 33–824 inhibited LH release through a central mechanism was confirmed using superfused median eminences in vitro. Thus FK 33–824 (1 μmol/l) greatly diminished the release of GnRH induced by the introduction of a depolarizing stimulus (36 mmol K+/l) in tissue obtained from both intact and ovariectomized ewe lambs. Since neurotransmitter levels in superfusate samples were below the limit of detection of the high-performance liquid chromatography assay, it remains to be ascertained whether FK 33–824 concomitantly affected neurotransmitter release. These results lead us to conclude that FK 33–824 inhibits the secretion of LH, but not prolactin, in intact and ovariectomized prepubertal ewe lambs. The action of FK 33–824 is mediated, at the level of the median eminence, through a reduction of GnRH release. It is tentatively suggested that FK 33–824 may exert this inhibitory effect by stimulating the release of 5-hydroxytryptamine. J. Endocr. (1988) 116, 403–411