LCAT facilitates transacylation of 17 beta-estradiol in the presence of HDL3 subfraction.
It has been shown that estrogens need to be metabolized to their hydrophobic estrogen ester derivatives to act as antioxidants in lipoproteins. Data suggest that 17beta-estradiol (E(2)) becomes esterified in LCAT-induced reactions and the esters are transported from HDL particles to LDL and VLDL particles by a CETP-dependent mechanism. In the present study we have further investigated the regulation of E(2) esterification by LCAT and focused on the importance of HDL structure and composition in the esterification process. Isolated LDL, HDL(2), HDL(3), and reconstituted discoidal HDL (rHDL) were incubated with labeled E(2), with and without purified LCAT, at 37 degrees C for 24 h. After purification of the lipoprotein fractions, there was a significant peak of radioactivity representing esterified estradiol attached to HDL(3) and rHDL, but HDL(2) and LDL contained only trace amounts of labeled estradiol ester. TLC analysis confirmed that the radioactivity migrated in a position corresponding to that of 17beta-E(2) 17-monoester standard. The amount of radioactivity associated with HDL(3) and rHDL representing esterified E(2) was significantly increased by addition of purified LCAT. However, only limited increases of radioactivity were observed in HDL(2) and LDL. In conclusion, HDL subfractions differ in their potential to regulate estradiol esterification by LCAT.
Höckerstedt
Anna
A
Department of Medicine, Helsinki University Central Hospital, FIN-00290, Helsinki, Finland.
Tikkanen
Matti J
MJ
Jauhiainen
Matti
M
D000215:Acylation; D000328:Adult; D008076:Cholesterol, HDL / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism; D002850:Chromatography, Gel / Q000379:methods; D003911:Dextrans / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D053439:Lipoproteins, HDL2; D053440:Lipoproteins, HDL3; D008297:Male; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*; D014316:Tritium / Q000302:isolation & purification / Q000378:metabolism
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003911:Dextrans; D008075:Lipoproteins, HDL; D053439:Lipoproteins, HDL2; D053440:Lipoproteins, HDL3; D014316:Tritium; D004958:Estradiol; C072350:estradiol 17-acetate; C025614:sephadex; D007862:Phosphatidylcholine-Sterol O-Acyltransferase