MECHANISM OF MELATONIN SIGNAL-TRANSDUCTION IN THE NEONATAL RAT PITUITARY

Melatonin inhibits GnRH-induced LH release from anterior pituitary of the neonatal rat. It acts via specific high affinity receptors and dec reases concentrations of intracellular calcium ([Ca2+](i)) and cyclic AMP. To determine which of these second messengers transduces the mela tonin inhibition of LH release, we have tested the effect of melatonin in the presence of specific drugs affecting either of these second me ssengers. Calcium channel antagonist nifedipine inhibited LH release f rom cultured pituitary to a similar degree as did melatonin and preven ted the inhibitory effect of melatonin on LH release. Calcium channel agonist Bay K potentiated the LH release and reduced the inhibitory ef fect of melatonin. This observation constitutes strong evidence that m elatonin inhibits LK release aia inhibition of calcium influx through voltage sensitive channels. The cyclic AMP derivative 8-bromo-cAMP pot entiated GnRH-stimulation of LH release but did not prevent the melato nin-induced inhibition of the release. However, when used in combinati on with low concentration of Bay K, which alone reduced the melatonin effect only partially, 8-bromo-cAMP completely blocked the melatonin e ffect. This observation suggests that both cAMP and [Ca2+](i) may be i nvolved in the effect of melatonin on LH release.