Melatonin inhibition of GnRH-induced LH release from neonatal rat gonadotroph: involvement of Ca2+ not cAMP.
Melatonin inhibits gonadotropin-releasing hormone-induced release of luteinizing hormone (LH) from the neonatal rat gonadotrophs. The second messenger involved is not known, although there are several candidates, including adenosine 3',5'-cyclic monophosphate (cAMP) and intracellular free Ca2+. The present study addresses the question of which second messenger mediates melatonin inhibition of LH release. We found that the effect of melatonin was not prevented by cAMP protagonists, including 8-bromo-cAMP, dibutyryl cAMP, 3-isobutyl-1-methylxanthine, and forskolin. However, treatments that enhanced Ca2+ influx masked the effects of melatonin, and treatments that blocked Ca2+ influx mimicked the effects of melatonin. Moreover, melatonin decreased K(+)-induced LH release, 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 involving inhibition of Ca2+ influx, and that cAMP does not seem to be involved in this effect of melatonin.
Vanecek
J
J
Institute of Physiology, Czech Academy of Sciences, Prague.
Klein
D C
DC
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002118:Calcium / Q000502:physiology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000502:physiology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008550:Melatonin / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D008550:Melatonin; D002118:Calcium