Background: We have previously shown that Estradiol (E2) increases heart weight, cardiomyocyte size and cardiac expression of growth factors in ovariectomized (ovx) mice as a model for hormone replacement therapy of menopausal women [1]. To investigate whether the phytoestrogen genistein (GEN) exerts a similar effect on heart physiology, ovx mice were treated for 3 months with various doses of GEN. To decipher which subtype of estrogen receptor (ER) mediates a putative estrogenic effect of GEN in the heart, ERα- and ERβ-knockout mice (KO) were treated with GEN.
Methods: 2 months old mice were ovx and randomly assigned to feed on diets with 7 different GEN doses (0.01, 0.03, 0.1, 0.3, 1, 3 and 10 g genistein/kg food) for 12 weeks. Mice with intact ovaries and ovx animals fed on soy-free diet were used as controls. At the end of treatment, uterus-, heart- and body weight were determined and cardiac expression of IGF1 was measured by qRT-PCR.
Results: OVX led to an increase in body weight, while the three highest GEN doses prevented this increase. Uterus weight was decreased in the ovx group and all GEN groups except for the 10 g/kg food group. The three highest GEN doses significantly increased heart-to-body-weight ratio compared to ovx mice. A similar effect was determined for cardiac IGF1 expression. The experiment was repeated with ovx ERα- and ERβ-KO-mice fed with a diet containing 1 g GEN/kg food. The estrogenic effect of GEN in the heart was maintained in ERß- but completely prevented in ERα-KO mice.
Conclusion: The present findings indicate that exposure of female mice to the isoflavone GEN influences body weight and cardiac mass and gene expression in a dose-dependent manner. This estrogenic effect is mediated via ERα.
References:
1 Nguyen BT, Kararigas G, Wuttke W, Jarry H. Long-term treatment of ovariectomized mice with estradiol or phytoestrogens as a new model to study the role of estrogenic substances in the heart. Planta Med. 2012 78: 6 – 11.
