A subpopulation of neonatal gonadotropin-releasing hormone-sensitive pituitary cells is responsive to melatonin.

Melatonin partially inhibits the GnRH-induced elevation of intracellular free Ca2+ ([Ca2+]i) and depolarization of the plasma membrane of neonatal rat GnRH-responsive pituitary cells. This effect is lost during development. In the present study, this line of investigation was extended using single cell analysis. This revealed that melatonin does not alter basal [Ca2+]i in GnRH-responsive cells, but it does inhibit the effect of GnRH on [Ca2+]i in approximately 40% of these cells. Complete inhibition is seen in only approximately 11% of the GnRH-sensitive cells. Analysis of membrane potential also indicated that melatonin hyperpolarizes only a subpopulation of neonatal GnRH-sensitive cells and reverses GnRH-induced depolarization. In the absence of extracellular Ca2+, this effect was greater and more frequently observed. Simultaneous analysis of membrane potential and [Ca2+]i in individual GnRH-treated cells indicated that melatonin altered both parameters in the same cell. This is consistent with the hypothesis that melatonin decreases [Ca2+]i by hyperpolarizing the cell, thereby inhibiting Ca2+ influx through voltage-sensitive channels. The finding that melatonin only acts on a subpopulation of GnRH-responsive cells probably explains why melatonin partially reverse the effects of GnRH in mixed population studies. The existence of a specific melatonin-sensitive population of cells raises the possibilities that the developmental loss of melatonin sensitivity might reflect their selective death or the decreased expression of melatonin receptors in these cells. In addition, it is possible that melatonin-sensitive GnRH-responsive cells might have other remarkable features, such as secretion of a biologically active substance not produced by melatonin-insensitive GnRH-responsive cells.