In neonatal rat gonadotrophs, melatonin inhibits several GnRH-induced effects: stimulation of LH release as well as the increase of several second messengers as cAMP, diacylglycerol and [Ca2+]i . Recently, GnRH has been shown to induce expression of immediate early genes of fos and jun family in adult rat gonadotrophs. The purpose of this study was to determine, whether melatonin inhibits the GnRH-induced induction of cFos in neonatal rat pituitary cells. The effects of GnRH and/or melatonin on cFos immunoreactivity was determined in primary cultures of neonatal rat pituitary cells attached to the coverslip. GnRH (3 nM) induced a time-dependent increase of cFos immunoreactivity in about 10 to 15% of the cultured cells. Significant increase was observed already 30 min after GnRH administration, the maximal increase occurred after about 60 min and then gradually decreased. Melatonin (100 nM) markedly attenuated the GnRH-induced increase. GnRH increased cFos immunoreactivity in the cells in a dose-dependent manner (EC50=36 pM) and melatonin (100 nM) attenuated the response at all GnRH concentrations tested. Melatonin had no effect on basal cFos immunoreactivity, but it inhibited the GnRH-induced (10 nM) increase of cFos in dose-dependent manner (EC50=12 pM). In conclusion, this is the first report showing the inhibitory effect of melatonin on gene transcriptional activity in gonadotrophs.