Copper induces luteinizing hormone release and desensitization of pituitary gonadotropes

Abstract

Copper stimulated LH release from cultured rat pituitary cells in a dose- and time-dependent manner. After 4 h of incubation with 10 μ M Cu 2+, LH release was stimulated by 3-fold. The release of LH stimulated by Cu 2+ was Ca 2+ dependent, thus excluding the possibility that the releasing activity of this divalent cation was due to a toxic effect on pituitary cells. The stimulatory action of Cu 2+ is substantially mediated via the GnRH-receptors since Cu 2+ inhibited 125I-Buserelin binding and since a GnRH-antagonist blocked most of the Cu 2+-stimulated LH release (80%). Both GnRH (1 μM) and Cu 2+ (10 μM) induced desensitization of pituitary cells to a subsequent stimulation of either GnRH (0.5 nM) or Cu 2+ (10 μM). However, in contrast to GnRH, Cu 2+ did not induce down regulation of GnRH receptors. These findings suggest that the Cu 2+ effects are mainly mediated through the GnRH receptors.