title: Genistein alters coagulation gene expression in ovariectomised rats treated with phytoestrogens.
abstract: Recent data has shown that hormone therapy (HT) increases the risk of cardiovascular and thromboembolic disease, particularly in users of oral HT. Phytoestrogens are popular alternatives to oestrogen therapy; however, their effects on cardiovascular risk are unknown. We investigated the effect of the phytoestrogen, genistein on the expression of genes and proteins from the haemostatic system in the liver in an ovariectomised rat model. Fifty-nine virgin female Sprague-Dawley rats were fed with soy-free chow supplemented with 17β estradiol (E2) (daily uptake 0.19 or 0.75 mg/kg body weight), or genistein (daily uptake 6 or 60 mg/kg body weight), for three months and compared to soy-free control rats. Gene expression of prothrombin, factor VII, fibrinogen alpha and fibrinogen beta was increased with E2 and genistein compared to the soy-free control group (p<0.001). Genistein increased factor VII significantly more than E2 (p<0.005). Plasminogen mRNA was increased in both treatment groups compared to the soy-free control, with genistein expression significantly higher than E2 (p<0.001). Tissue plasminogen inhibitor (tPA), plasminogen activator inhibitor-1 (PAI-1) and C-reactive protein (CRP) expression were also increased in both groups relative the soy-free control. Results of protein analysis largely concurred with those of the mRNA. Oestrogen receptor β (ERβ) was undetected while oestrogen receptor α (ERα) was detected in each sample group. Genistein can increase the expression of coagulation and fibrinolytic genes. This effect was similar and in some cases higher than 17β estradiol. These results suggest that genistein may not be neutral with respect to the haemostatic system.
authors.affiliation: Coagulation Research Laboratory, Dept of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St James Hospital, Dublin, Ireland.
authors.forename: Lynne A
authors.initials: LA
authors.lastname: Kelly
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Leary
authors.forename: Dana
authors.initials: D
authors.lastname: Seidlova-Wuttke
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wuttke
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Norris
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015914:Estrogen Replacement Therapy; D005167:Factor VII / Q000235:genetics / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010052:Ovariectomy; D048789:Phytoestrogens / Q000494:pharmacology*; D010958:Plasminogen / Q000235:genetics / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D011516:Prothrombin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism
chemical_list: D048789:Phytoestrogens; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C464794:fibrinogen Aalpha; D005167:Factor VII; D011516:Prothrombin; D005340:Fibrinogen; D010958:Plasminogen; D002097:C-Reactive Protein; D019833:Genistein; D010959:Tissue Plasminogen Activator