Regulation of low-density lipoprotein receptor activity by estrogens and phytoestrogens in a HepG2 cell model.
OBJECTIVE
Estrogen treatment is thought to lower low-density lipoprotein (LDL) cholesterol levels by increasing clearance through hepatic LDL receptors. This study aimed to determine the effect of estrogens and phytoestrogens on LDL receptor activity in a human hepatoma cell line, HepG2.


METHODS
HepG2 cells in culture were incubated for 24 h with estrogen or phytoestrogen and LDL receptor activity was measured by examining the cellular binding of colloidal gold-labelled LDL.


RESULTS
17Beta-estradiol significantly increased LDL receptor activity whereas estriol had negligible effects. Incubation with the isoflavonoids, formononetin, biochanin A and daidzein, caused significant elevations in receptor activity at concentrations above 40 microM. Coumestrol, a coumestan with a high level of estrogenic activity, caused a 3-fold increase in receptor activity at a concentration of 50 microM. Of the phytoestrogenic mammalian lignans enterolactone and enterodiol, only enterolactone displayed the ability to significantly upregulate LDL receptor activity at 50 microM.


CONCLUSIONS
This study suggests that the LDL receptor-stimulating effect of natural estrogens is mainly due to estradiol and that the cholesterol-lowering effect of diets high in phytoestrogens may be due in part to their ability to increase hepatic LDL receptor activity.
Department of Physiology, University of Adelaide, Australia. alice_owen@uow.edu.au
Alice J
AJ
Owen
Paul D
PD
Roach
Mavis
M
Abbey
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002460:Cell Line; D008078:Cholesterol, LDL / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D048789:Phytoestrogens / Q000494:pharmacology*; D011973:Receptors, LDL / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D008078:Cholesterol, LDL; D004967:Estrogens; D048789:Phytoestrogens; D011973:Receptors, LDL; D004958:Estradiol