Biomedical subjects

Anna Höckerstedt

Publications and source records attributed to Anna Höckerstedt.

4 recordsLinked to original sources

PubMed2005

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.

Esterification↗

PubMed2004

Lecithin/cholesterol acyltransferase induces estradiol esterification in high-density lipoprotein, increasing its antioxidant potential.

Endogenous estrogens protect against atherosclerosis, but the exact mechanisms remain unclear. One possibility is inhibition of lipoprotein oxidation. To act as antioxidants, estrogens reportedly need to be converted to lipophilic estrogen fatty acyl esters in a reaction catalyzed by lecithin/cholesterol acyltransferase (LCAT). To demonstrate directly that estradiol (E2) esters formed by LCAT and incorporated in high-density lipoprotein (HDL) increase its antioxidant potential, we investigated the copper-induced oxidation of purified HDL after incubations of: 1) HDL alone; 2) HDL in the presence of exogenous E2; 3) HDL in the presence of exogenous LCAT; 4) HDL in the presence of both E2 and LCAT; and 5) HDL in the presence of E2, LCAT, and the LCAT inhibitor DTNB. We used this in vitro model system with supraphysiological concentrations of E2 and purified LCAT to produce E2 ester-containing HDL particles for studies of oxidation resistance. The lag time of HDL oxidation significantly increased with increasing contents of HDL-associated E2 esters. In conclusion, our results clearly demonstrated the role of LCAT in E2 esterification and its involvement in antioxidant protection of HDL. Elucidation of the possible in vivo role of HDL-associated estrogen esters requires further critical studies including experiments with physiological hormone concentrations.

Antioxidants↗

PubMed2002

Lipoprotein-associated estrogens.

The discovery of a family of hormonal steroids esterified with fatty acid has raised questions concerning their physiologic role. Because of their water-insolubility these compounds are present in the circulation only as components of lipoprotein particles. Current evidence supports the hypothesis that estrogen esterification is catalyzed by lecithin:cholesterol acyltransfearse associated with HDL. In addition, recent results indicate that estradiol esters are transferred from HDL to LDL particles in a cholesteryl ester transfer protein (CETP)-associated process. The studies now focus on the various possible physiologic roles proposed for these hormone derivatives, (1) functioning as fat-soluble antioxidants incorporated in lipoproteins rendering protection against oxidation of these particles, (2) providing a mechanism for hormonal storage in lipoproteins and fat tissues, (3) providing a novel hormone transport system using lipoprotein as carriers and lipoprotein receptors for entry into cells. Quantitative methods of determination of estradiol fatty acid esters in human body fluids have been developed. Preliminary studies suggest that diet-derived plant estrogens may also form fat-soluble derivatives which become incorporated in lipoproteins.

Antioxidants↗

PubMed2002

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.

Acylation↗