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  • Title: Regulation of low-density lipoprotein receptor activity by estrogens and phytoestrogens in a HepG2 cell model.
    Author: Owen AJ, Roach PD, Abbey M.
    Journal: Ann Nutr Metab; 2004; 48(4):269-75. PubMed ID: 15331887.
    Abstract:
    BACKGROUND/AIMS: 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. CONCLUSION: 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.
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