17 beta-estradiol inhibits LDL oxidation and cholesteryl ester formation in cultured macrophages.

The effects of 17 beta estradiol, testosterone, the estradiol benzoate, and probucol on the oxidation kinetics of low density lipoprotein (LDL) in vitro in absorption presence of 10 microM Cu (II) are examined. Changes in the absorption at 234 nm (A234) and fluorescence (Ex340/Em420) are monitored. The kinetics of the changes observed let us suggest a precursor-product relationship between dienes and fluorochromes in the oxidized LDL. The addition of 17 beta estradiol and probucol to LDL results in a prolongation of the lag phase characterized by only insignificant formation of dienes and fluorochromes. The addition of testosterone and estradiol benzoate used as control compounds has no effect on the lag phase and thus no LDL stabilizing effect. Conditioned LDL which was incubated in F-10 medium before exposure to cultured P388D.1 macrophages increases the formation of cytoplasmic lipid droplets and of cellular cholesteryl esters. The LDL stabilizing compounds beta estradiol and probucol (but not testosterone) causes a reduction of the cholesteryl ester content of the cultured macrophages. Protection of LDL particles against oxidative damage apparently results also in lowering of cytoplasmic cholesteryl ester in cultured P388D.1 cells. We conclude that the known antiatherosclerotic potency of 17 beta estradiol may in part result from its LDL stabilizing activity.