Genistein alters coagulation gene expression in ovariectomised rats treated with phytoestrogens

Lynne A. Kelly; John J. O’Leary; Dana Seidlova-Wuttke; Wolfgang Wuttke; Lucy A. Norris

doi:10.1160/TH10-03-0201

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 104(06): 1250-1257
DOI: 10.1160/TH10-03-0201

Animal Models

Schattauer GmbH

Genistein alters coagulation gene expression in ovariectomised rats treated with phytoestrogens

Lynne A. Kelly

¹Coagulation Research Laboratory, Dept of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St. James Hospital, Dublin, Ireland

,

John J. O’Leary

²Dept of Pathology, Trinity Centre for Health Sciences, St. James Hospital, Dublin, Ireland

,

Dana Seidlova-Wuttke

³Department of Endocrinology, University Medical Center, Göttingen, Göttingen, Germany

,

Wolfgang Wuttke

³Department of Endocrinology, University Medical Center, Göttingen, Göttingen, Germany

,

Lucy A. Norris

¹Coagulation Research Laboratory, Dept of Obstetrics and Gynaecology, Trinity Centre for Health Sciences, St. James Hospital, Dublin, Ireland

› Author Affiliations

Abstract

Summary

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 up-take 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.

Keywords

Haemostasis - phytoestrogen - menopause - thrombosis

Full Text

References

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