ESTRADIOL AS AN ANTIOXIDANT - INCOMPATIBLE WITH ITS PHYSIOLOGICAL CONCENTRATIONS AND FUNCTION

Estradiol has been documented to inhibit the oxidation of low density lipoprotein (LDL), We show that physiological concentrations of estrad iol do not inhibit the oxidation of LDL by copper, LDL samples isolate d from a) premenopausal and postmenopausal women and from b) women at different time periods during their menstrual cycle, who differ vastly in plasma estradiol levels, were also oxidized at the same rates by c opper. In contrast, LDL samples isolated from c) women who were hypers timulated during in vitro fertilization (IVF), with estradiol concentr ations above 2000 pg/ml, were resistant to oxidation by copper. Howeve r, these LDL samples were also oxidized at a higher rate by peroxidase s, More importantly, subjects with high estradiol levels also showed a n increase in myeloperoxidase (MPO) protein in the plasma.jlr Based on these results, we conclude that at physiologic concentrations, it is unlikely that estradiol could act as an antioxidant, In fact, the abil ity of estradiol to induce MPO and become a prooxidant might instead s uggest that MPO-mediated oxidative clearance of LDL from plasma by liv er might favorably influence the outcome of atherosclerosis.