Copper stimulates the release of luteinizing hormone releasing hormone from isolated hypothalamic granules

Copper, administered to female rabbits, stimulates LHRH release into the hypophyseal portal blood (5) and induces ovulation (1-3). To gain further understanding of the mechanism of action of copper, in this study we addressed the question: Does copper, in the form of CuATP, stimulate LHRH release from isolated hypothalamic granules? Isolated hypothalamic granules, obtained from adult male rats, were incubated under in vitro conditions in the absence (control) or presence of CuATP (0.1 - 2.5 mM). In the presence of CuATP, we noted that LHRH release was stimulated, and the magnitude of stimulation was a saturable function of the concentration of copper, being maximal at 2.5 mM. In addition, we compared the effects of a series of divalent cations (Cu, Zn, Mg, Ca, Fe, Ba, Sr, Mn; 2.5 mM each) on LHRH release and found that copper stimulated release seventeenfold, zinc--sixfold, and the other divalent cations--twofold or less. Thus, copper appears to be a unique releaser of LHRH, and it may act at the level of the LHRH granule.