Melatonin modulates cAMP signaling in rat epididymal epithelial cells

Abstract

Melatonin, a pineal neurohormone, has been implicated in the regulation of a variety of biological processes such as circadian rhythmicities and reproductive functions. Our laboratory has successfully identified high affinity melatonin binding sites in the corpus epididymidis of rats. This observation has provided us with a unique opportunity to define the effects of melatonin on various signal transduction pathways in male reproductive tissues. The effects of melatonin on cAMP levels in rat corpus epididymis were investigated. Melatonin was found to inhibit, concentration-dependently, forskolin-stimulated cAMP accumulation in epididymal epithelial cells via pertussis toxin-sensitive Gi protein-coupled receptors. This inhibitory action of melatonin on forskolin-stimulated cAMP was potentiated by 5α-dihydrotestosterone. The stimulation of adenylyl cyclase by isoproterenol or norepinephrine was attenuated by melatonin. In situ hybridization studies have identified functional melatonin MEL1A and MEL1B receptors in rat epididymal epithelial cells. The effects of different melatonin analogues on adenylyl cyclase activity of rat epididymal epithelial cells were also studied. Our data support a modulatory action of melatonin, mediated via pertussis toxin-sensitive Gi-coupled MEL1A and MEL1B receptors, in the regulation of rat epididymal epithelial cell physiology.