Cellular mechanism of melatonin action in neonatal rat pituitary.
Melatonin inhibits gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) release from neonatal rat anterior pituitary. Melatonin has been shown to decrease the concentration of several second messengers in neonatal pituitary, but it is not known which of them transduces the melatonin effect on LH release. In order to determine the mechanism of melatonin action, we tested the effect of melatonin on GnRH-induced LH release in the presence of specific drugs affecting second messengers. The calcium channel antagonist nifedipine inhibited LH release from cultured pituitary to a similar degree as melatonin and prevented the inhibitory effect of melatonin on LH release. The calcium channel agonist Bay K potentiated the GnRH-stimulated LH release and reduced the inhibitory effect of melatonin on LH release. These data strongly suggest that melatonin inhibits LH release via inhibition of calcium influx through voltage-sensitive channels. The cyclic AMP (cAMP) derivative 8-bromo-cAMP potentiated GnRH stimulation of LH release but did not prevent the melatonin-induced inhibition of LH release. However, when used in combination with Bay K, which reduced only partially the melatonin effect by itself, 8-bromo-cAMP completely blocked the melatonin effect. This observation suggests that decreased cAMP accumulation may also be involved in transduction of the melatonin effect on LH release.
Vanecek
J
J
Institute of Physiology, Academy of Sciences of Czech Republic, Prague.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D004357:Drug Synergism; D004789:Enzyme Activation; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D007986:Luteinizing Hormone / Q000378:metabolism*; D008550:Melatonin / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015124:8-Bromo Cyclic Adenosine Monophosphate; D007987:Gonadotropin-Releasing Hormone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D007986:Luteinizing Hormone; D011493:Protein Kinase C; D009543:Nifedipine; D008550:Melatonin; D013755:Tetradecanoylphorbol Acetate