Melatonin suppresses the induction of AP-1 transcription factor components in the pars tuberalis of the pituitary

In ovine pars tuberalis cells which express high affinity Mel la melatonin receptors, the ability of melatonin to directly stimulate or inhibit AP-1 transcription factor gene expression was studied. Effects of melatonin upon mRNA expression by forskolin, serum and IGF-1 were also investigated. Northern analysis showed melatonin had no direct stimulatory nor inhibitory effect upon transcription or translation. Melatonin was able to significantly inhibit forskolin-stimulated induction of c-fos and jun B mRNA whilst forskolin had no effect upon c-jun or jun D. Induction of c-Fos translation by forskolin was also inhibited by melatonin. Serum induced c-fos and c-jun, but melatonin was unable to affect these changes. Similarly IGF-1 stimulated c-fos and melatonin had no effect upon this induction. From these results it can be concluded that melatonin has no independent effects on expression of the AP-1 genes, rather its primary function is to inhibit cell activities through cyclic AMP-dependent routes of gene activation.