Copper and thiol regulation of gonadotropin releasing hormone binding and luteinizing hormone release

The effects of copper, sulfhydryl and disulfide reagents on gonadotropin, releasing hormone (GnRH) binding to pituitary membrane preparations and on luteinizing hormone (LH) release from pituitaries of immature female rats were studied. Copper ions reduced the specific binding of 125I-labeled [D-Ser(t-Bu)6, des-Gly10-ethylamide]GnRH (Buserelin) to pituitary membranes in a dose responsive manner. Fifty percent inhibition of the specific binding was obtained at 3 x 10(-5)M Cu+2. The decreased binding stems from a 8-fold decrease in the apparent affinity of Buserelin, in the presence of copper ions. Cupric sulfate was examined for its ability to affect basal and GnRH stimulated LH release. Copper stimulated basal LH release 18-fold and 8-fold at 10(-4)M and 10(-5)M, respectively. The LH release in response to Cu+2 was calcium dependent. The effect of Cu+2 on GnRH stimulated LH release was a combined effect of Cu+2 on GnRH binding. GnRH on LH release and Cu+2 on LH release. N-ethylmaleimide, hydrogen peroxide and dithiothreitol did not alter significantly the specific binding of 125I-labeled Buserelin. N-ethylmaleimide and hydrogen peroxide did not affect GnRH stimulated LH release, whereas dithiothreitol (1 mM) significantly inhibited GnRH stimulated LH release. The present findings may explain the induction of ovulation by copper and the reduction in serum LH after injection of reducing agents.