Estradiol fatty acid esterification is increased in high density lipoprotein subclass 3 isolated from hypertriglyceridemic subjects.
Estrogen fatty acid esters are potent lipophilic estrogens transported exclusively in lipoproteins. They are formed in HDL in a reaction catalyzed by LCAT which is considered a prerequisite for their antioxidative action. Our previous studies in normotriglyceridemic (NTG) individuals demonstrated that estradiol (E2) esterification occurred mainly in HDL3 causing accumulation of esterified, but not of unesterified E2 in the lipoprotein particles. Using HDL obtained from hypertriglyceridemic (HTG) patients, we now investigated the effect of altered HDL composition on E2 esterification. Ultracentrifugally isolated HDL2 and HDL3 from NTG- and HTG-males were incubated in an in vitro model system with radioactive and with supraphysiological concentrations of non-radioactive E2 with and without exogenous LCAT. After purification, copper-induced oxidation of HDL was measured by monitoring conjugated diene formation. The results demonstrated that (i) E2 esterification occurring mainly in HDL3 was significantly more efficient in HTG-HDL3 compared to NTG-HDL3, (ii) triglyceride content in HDL3 correlated positively with E2 esterification rate, and (iii) addition of both exogenous LCAT and E2 into the incubation prolonged lag time of HDL3 oxidation. Thus, HDL composition regulates LCAT-facilitated E2 esterification but the in vivo role of this finding can be verified only in experiments using physiological hormone concentrations.
Höckerstedt
Anna
A
Department of Medicine, Division of Cardiology, Helsinki University Central Hospital, FIN-00290 Helsinki, Finland. anna.hockerstedt@hus.fi
Jauhiainen
Matti
M
Tikkanen
Matti J
MJ
D004951:Esterification; D004958:Estradiol / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000378:metabolism*; D066298:In Vitro Techniques; D008075:Lipoproteins, HDL / Q000097:blood*; D053440:Lipoproteins, HDL3; D008297:Male; D010084:Oxidation-Reduction; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism
D005227:Fatty Acids; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D004958:Estradiol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase