Melatonin action in neonatal gonadotrophs.
Neonatal pituitary cells express MT1 and MT2 subtype of melatonin receptors that are coupled to pertussis toxin-sensitive G proteins. Their activation by melatonin leads 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 have revealed that a reduction in gonadotropin release results from melatonin-induced inhibition of GnRH-stimulated calcium signaling. Melatonin inhibits both calcium influx through voltage-dependent calcium channels and calcium mobilization from intracellular stores. Inhibition of calcium influx, probably in a cAMP/protein kinase C-dependent manner, and the accompanying calcium-induced calcium release from ryanodine-sensitive intracellular pools by melatonin results in a delay of GnRH-induced calcium signaling. Melatonin-induced attenuation of GnRH-induced and inositol (1,4,5)-trisphosphate-mediated calcium release from intracellular pools attenuates the amplitude of calcium signal. 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 plasma gonadotropin levels. During the development, such tonic inhibitory effects of melatonin on GnRH action gradually decline due to a decrease in expression of functional melatonin receptors. In adult animals, melatonin does not have obvious direct effects on pituitary functions, whereas the connections 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.
Balík
A
A
Department of Cellular and Molecular Neuroendocrinology, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Kretschmannová
K
K
Mazna
P
P
Svobodová
I
I
Zemková
H
H
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D006062:Gonadotropins / Q000378:metabolism; D006801:Humans; D008550:Melatonin / Q000502:physiology*; D010902:Pituitary Gland / Q000378:metabolism*; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism*; D044123:Receptor, Melatonin, MT2 / Q000378:metabolism*; D011966:Receptors, LHRH / Q000378:metabolism; D012098:Reproduction / Q000502:physiology; D015398:Signal Transduction
D006062:Gonadotropins; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D011966:Receptors, LHRH; D008550:Melatonin