A SUBPOPULATION OF NEONATAL GONADOTROPIN-RELEASING HORMONE-SENSITIVE PITUITARY-CELLS IS RESPONSIVE TO MELATONIN

Melatonin partially inhibits the GnRH-induced elevation of intracellul ar free Ca2+ ([Ca2+]i) and depolarization of the plasma membrane of ne onatal rat GnRH-responsive pituitary cells. This effect is lost during development. In the present study, this line of investigation was ext ended using single cell analysis. This revealed that melatonin does no t alter basal [Ca2+]i in GnRH-responsive cells, but it does inhibit th e effect of GnRH on [Ca2+]i in approximately 40% of these cells. Compl ete inhibition is seen in only approximately 11% of the GnRH-sensitive cells. Analysis of membrane potential also indicated that melatonin h yperpolarizes only a subpopulation of neonatal GnRH-sensitive cells an d reverses GnRH-induced depolarization. In the absence of extracellula r Ca2+, this effect was greater and more frequently observed. Simultan eous analysis of membrane potential and [Ca2+]i in individual GnRH-tre ated cells indicated that melatonin altered both parameters in the sam e cell. This is consistent with the hypothesis that melatonin decrease s [Ca2+]i by hyperpolarizing the cell, thereby inhibiting Ca2+ influx through voltage-sensitive channels. The finding that melatonin only ac ts on a subpopulation of GnRH-responsive cells probably explains why m elatonin partially reverse the effects of GnRH in mixed population stu dies. The existence of a specific melatonin-sensitive population of ce lls raises the possibilities that the developmental loss of melatonin sensitivity might reflect their selective death or the decreased expre ssion of melatonin receptors in these cells. In addition, it is possib le that melatonin-sensitive GnRH-responsive cells might have other rem arkable features, such as secretion of a biologically active substance not produced by melatonin-insensitive GnRH-responsive cells.