Copper induces luteinizing hormone release and desensitization of pituitary gonadotropes.
Copper stimulated LH release from cultured rat pituitary cells in a dose-and time-dependent manner. After 4 h of incubation with 10 mu M Cu2+, LH release was stimulated by 3-fold. The release of LH stimulated by Cu2+ was Ca2+ 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 Cu2+ is substantially mediated via the GnRH-receptors since Cu2+ inhibited 125I-Buserelin binding and since GnRH-antagonist blocked most of the Cu2+-stimulated LH release (80%). Both GnRH (1 microM) and Cu2+ (10 microM) induced desensitization of pituitary cells to a subsequent stimulation of either GnRH (0.5 nM) or Cu2+ (10 microM). However, in contrast to GnRH, Cu2+ did not induce down regulation of GnRH receptors. These findings suggest that the Cu2+ effects are mainly mediated through the GnRH receptors.
D000818:Animals; D002064:Buserelin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003300:Copper / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007986:Luteinizing Hormone / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D011966:Receptors, LHRH; D013997:Time Factors
D011956:Receptors, Cell Surface; D011966:Receptors, LHRH; D003300:Copper; D007986:Luteinizing Hormone; D002064:Buserelin; D002118:Calcium