ABSTRACT
Pituitary cells from neonatal animals express functional MT1 subtype of melatonin receptorsthat signal through pertussis toxin-sensitive G proteins. Their activation by melatoninleads to a decrease in cAMP production and activity of protein kinase A, and attenuation of gonadotropin-releasing hormone (GnRH)-induced gonadotropin secretion. Single cell calcium and electrophysiological recordings revealed that reduction in gonadotropin release results from melatonin-induced inhibition of GnRH-stimulated calcium signaling. Melatonin inhibits both components of calcium signaling in gonadotrophs, calcium influx through voltage-dependent calcium channels and inositol (1,4,5)-trisphosphate-mediated calcium release from intracellular stores. Inhibition of calcium influx and the accompanied calcium-induced calcium release from ryanodine-sensitive intracellular pools by melatonin results in a delay of GnRH-induced calcium signaling. On the other hand, attenuation in GnRH-induced calcium release affects the amplitude of calcium signals. The potent inhibition of GnRH-induced calcium signaling and gonadotropin secretion by melatonin provides an effective mechanism to protect premature initiation of pubertal changes that are dependent on gonadotropin plasma levels. During the development, the tonic inhibitory effects of melatonin on GnRH action gradually attenuate, due to a decline in expression of functional melatonin receptors and changes in GnRH receptor signaling pathways. In adult animals, melatonin does not affect pituitary functions directly, whereas the coupling between melatonin release and hypothalamic functions, including GnRH release, are preserved, and are critically important in synchronizing the external photoperiods and reproductive functions through still not well characterized mechanisms.
