MELATONIN INHIBITION OF GNRH-INDUCED LH-RELEASE FROM NEONATAL RAT GONADOTROPH - INVOLVEMENT OF CA2+ NOT CAMP

Melatonin inhibits gonadotropin-releasing hormone-induced release of l uteinizing hormone (LH) from the neonatal rat gonadotrophs. The second messenger involved is not known, although there are several candidate s, including adenosine 3',5'-cyclic monophosphate (cAMP) and intracell ular free Ca2+. The present study addresses the question of which seco nd messenger mediates melatonin inhibition of LH release. We found tha t the effect of melatonin was not prevented by cAMP protagonists, incl uding 8-bromo-cAMP, dibutyryl cAMP, 3-isobutyl-1-methylxanthine, and f orskolin. However, treatments that enhanced Ca2+ influx masked the eff ects of melatonin, and treatments that blocked Ca2+ influx mimicked th e effects of melatonin. Moreover, melatonin decreased K+-induced LH re lease, which is dependent on Ca2+ influx but did not block release of LH due to thapsigargin-induced mobilization of Ca2+ from intracellular stores. These findings indicate that melatonin inhibits gonadotropin- releasing hormone-induced LH release, primarily through an action invo lving inhibition of Ca2+ influx, and that cAMP does not seem to be inv olved in this effect of melatonin.