Accumulation of high-density lipoprotein-derived estradiol-17beta fatty acid esters in low-density lipoprotein particles.
Estrogens are known to be powerful antioxidants in lipid-aqueous systems, as demonstrated by their inhibition of low-density lipoprotein (LDL) oxidation in vitro. Studies reporting that endogenous human estrogens could be rendered fat-soluble by esterification with fatty acids in vivo, and the subsequent detection of such esters in blood and fat tissue suggested a possible mechanism explaining how estrogens might protect LDL. Because of their lipophilicity, esterified estrogens may become incorporated in the lipoprotein structure, providing antioxidant potential for the particles. We incubated labeled 17beta-estradiol with ovarian follicular fluid and with plasma in the absence and presence of the LCAT inhibitor DTNB. This was followed by ultracentrifugal isolation of LDL and high-density lipoprotein and analysis of the radioactive label in the "ester" and "free" fractions purified from these lipoproteins. The results indicated that LCAT-mediated synthesis of esterified 17beta-estradiol occurred in high-density lipoprotein particles, and suggested a novel cholesterol ester transfer protein-mediated mechanism for their transfer to LDL particles.
Department of Medicine, University of Helsinki, 00014 Helsinki, Finland.
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Helisten
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Höckerstedt
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Wähälä
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Tiitinen
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Adlercreutz
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Jauhiainen
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Tikkanen
D002352:Carrier Proteins / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004951:Esterification; D004958:Estradiol / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D015571:Follicular Fluid / Q000378:metabolism*; D006023:Glycoproteins; D006801:Humans; D008075:Lipoproteins, HDL / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000032:analysis / Q000378:metabolism*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000037:antagonists & inhibitors; D014316:Tritium; D014461:Ultracentrifugation
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014316:Tritium; D004958:Estradiol; D004228:Dithionitrobenzoic Acid; D007862:Phosphatidylcholine-Sterol O-Acyltransferase