Estrogens inhibit copper and cell-mediated modification of low density lipoprotein.

The effects of estrogens on LDL modification by copper ions, U 937 monocyte-like cells or endothelial cells was studied by determination of the lipid peroxidation product content and measurement of the relative electrophoretic mobility. The presence of estradiol, estriol and estrone inhibited LDL oxidation in a dose-dependent manner in the range of concentrations from 5 to 50 microM. In the case of oxidation by Cu2+, the decreasing order of efficiency was: estradiol, estriol, estrone. In monocyte-induced oxidation, the protective effect of estrogens was more marked, and the order of efficiency was the same, except that estrone was as active as estriol. Pretreatment of monocyte cells with estrogens also inhibited the subsequent modification of LDL by these cells, tested in the absence of the hormones. Testosterone had no effect in all the studied systems. Furthermore, the degradation by J774 macrophage like cells of LDL modified either by Cu2+ or monocytes was markedly reduced when modification has been performed in the presence of estrogens. Since oxidative modification of LDL is believed to be involved in the appearance of atherosclerotic plaques, this effect of estrogens might be related to their protective action against atherosclerosis.