Antioxidant protection of LDL by physiologic concentrations of estrogens is specific for 17-beta-estradiol

Risk for coronary artery disease is reduced by exposure to estrogens, although the mechanisms of protection are not fully defined. Recent observations have shown that physiologic concentrations of 17-beta-estradiol (E-2) exhibit antioxidant activity in vitro, slowing the formation of atherogenic, oxidized low-density lipoprotein (LDL). Using concentrations physiologically relevant for premenopausal women, we compared the antioxidant potency of estrone (E-1), E-2, and estriol (E-3) as measured by their ability to inhibit LDL oxidation. Plasma was incubated with 10 nmol/l estrogens for 4 h at 37 degrees C, followed by LDL isolation and Cu2+-mediated oxidation in conjugated diene assays. Only E-2 demonstrated antioxidant activity at these physiologic concentrations. Resistance to oxidation was not associated with sparing of endogenous alpha-tocopherol during plasma incubations. Incubation of plasma with radiolabeled estrogens yielded similar association of E-1 and E-2 with LDL which was 5-8-fold greater than the association of E-3. Chromatographic analysis revealed the association of authenic E-1 with LDL, while plasma-derived E-2 esters were the major form of E-2 associated with LDL which was resistant to oxidation. Thus, conjugation in plasma and association of E-2 esters with LDL appear to be specific for E-2 among these estrogens and render this LDL resistant to oxidation by Cu2+. This antioxidant activity may be another means whereby E-2 protects against coronary artery disease in women. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.