title: Estrogen receptor alpha augments changes in hemostatic gene expression in HepG2 cells treated with estradiol and phytoestrogens.
abstract: Phytoestrogens are popular alternatives to estrogen therapy however their effects on hemostasis in post-menopausal women are unknown. The aim of this study was to determine the effect of the phytoestrogens, genistein, daidzein and equol on the expression of key genes from the hemostatic system in human hepatocyte cell models and to determine the role of estrogen receptors in mediating any response seen. HepG2 cells and Hep89 cells (expressing estrogen receptor alpha (ERα)) were incubated for 24 h with 50 nM 17β-estradiol, genistein, daidzein or equol. Tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), Factor VII, fibrinogen γ, protein C and protein S mRNA expression were determined using TaqMan PCR. Genistein and equol increased tPA and PAI-1 expression in Hep89 cells with fold changes greater than those observed for estradiol. In HepG2 cells (which do not express ERα), PAI-1 and tPA expression were unchanged. Increased expression of Factor VII was observed in phytoestrogen treated Hep89 cells but not in similarly treated HepG2s. Prothrombin gene expression was increased in equol and daidzein treated HepG2 cells in the absence of the classical estrogen receptors. These data suggest that phytoestrogens can regulate the expression of coagulation and fibrinolytic genes in a human hepatocyte cell line; an effect which is augmented by ERα.
authors: Coagulation Research Laboratory, Department of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St. James Hospital, Dublin 8, Ireland. Electronic address: kellyl37@tcd.ie.
authors: Lynne A
authors: LA
authors: Kelly
authors: Department of Endocrinology, University Medical Center Göttingen, Georg-August-University Göttingen, Germany.
authors: Dana
authors: D
authors: Seidlova-Wuttke
authors: Department of Endocrinology, University Medical Center Göttingen, Georg-August-University Göttingen, Germany.
authors: Wolfgang
authors: W
authors: Wuttke
authors: Department of Histopathology, Trinity College Dublin, Ireland.
authors: John J
authors: JJ
authors: O'Leary
authors: Coagulation Research Laboratory, Department of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St. James Hospital, Dublin 8, Ireland.
authors: Lucy A
authors: LA
authors: Norris
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects / Q000235:genetics*; D060754:Equol / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005167:Factor VII / Q000235:genetics / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D006490:Hemostatics / Q000494:pharmacology*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D048789:Phytoestrogens / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D011516:Prothrombin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D006490:Hemostatics; D007529:Isoflavones; D048789:Phytoestrogens; D010936:Plant Extracts; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D004958:Estradiol; D060754:Equol; C004742:daidzein; D005167:Factor VII; D011516:Prothrombin; D005337:Fibrin; D019833:Genistein; D010959:Tissue Plasminogen Activator
keywords: ERα; Genistein; Hemostasis; Phytoestrogen