INHIBITORY EFFECT OF MELATONIN ON GONADOTROPIN-RELEASING HORMONE-INDUCED CA2-CELLS OF NEWBORN RATS( OSCILLATIONS IN PITUITARY)

The effect of melatonin on the gonadotropin-releasing-hormone (GnRH)-i nduced oscillatory rises in intracellular calcium concentration, [Ca2](i), was studied in cultured cells from the anterior pituitary gland of 6- to 8-day-old rats, GnRH-induced [Ca2+](i) oscillations were reco rded indirectly by monitoring the activity of apamin-sensitive Ca2+-ac tivated K+ channels using the perforated patch-clamp technique and fas t microperfusion system. Melatonin (In;li) inhibited the initiation or attenuated the amplitude of oscillatory current responses induced by 10 nM GnRH in 72% of GnRH-sensitive cells, Analysis of the melatonin d ose-inhibition relationship showed that melatonin inhibited the initia tion of [Ca2+](i) oscillations with IC50 = 0.35 nM. In partially inhib ited cells, melatonin reduced the GnRH-induced current amplitude by 55 % on the average, prolonged the delay in onset of response to GnRH and decreased the frequency of oscillations. Once initiated by GnRH, the amplitude and frequency of oscillatory currents was inhibited by melat onin after a latency of 10-30 s. These effects of melatonin were fully reversible. After pretreatment of neonatal gonadotropes with pertussi s toxin, no inhibition by melatonin was observed. The inhibitory effec t of melatonin on initiation, amplitude and frequency of GnRH-induced oscillatory current persisted in the absence of external Ca2+. Melaton in alone did not induce any transmembrane current or membrane potentia l changes. These observations suggest that melatonin reduces GnRH-indu ced calcium mobilization from intracellular stores.