Accumulation of high-density lipoprotein-derived estradiol-17 beta fatty acid esters in low-density lipoprotein particles

Estrogens are known to be powerful antioxidants in lipid-aqueous systems, a s demonstrated by their inhibition of low-density lipoprotein (LDL) oxidati on in vitro. Studies reporting that endogenous human estrogens could be ren dered fat-soluble by esterification with fatty acids in vivo, and the subse quent detection of such esters in blood and fat tissue suggested a possible mechanism explaining how estrogens might protect LDL. Because of their lip ophilicity, esterified estrogens may become incorporated in the lipoprotein structure, providing antioxidant potential for the particles. We incubated labeled 17 beta -estradiol with ovarian follicular fluid and with plasma i n the absence and presence of the LCAT inhibitor DTNB. This was followed by ultracentrifugal isolation of LDL and high-density lipoprotein and analysi s of the radioactive label in the "ester" and "free" fractions purified fro m these lipoproteins. The results indicated that LCAT-mediated synthesis of esterified 17 beta -estradiol occurred in high density lipoprotein particl es, and suggested a novel cholesterol ester transfer protein-mediated mecha nism for their transfer to LDL particles.