Dose dependent effects of genistein on gene expression in the heart of ovariectomized mice after long term treatment.
Abstract. 52 Symposium der Deutschen Gesellschaft für Endokrinologie, März 2009, Giessel Germany.
Objectives: Both types of estrogen receptors are expressed in cardiomyocytes. Epidemiological data show that phytoestrogens like genistein (GEN) ameliorate menopausal symptoms. Surprisingly, little data are available regarding effects of GEN in the heart. To treat symptoms of estrogen deficiency, women take GEN for prolonged time. To simulate the usage in the human, we conducted a long term study with mice to examine putative estrogenic effects of GEN in the heart. Mice were fed with GEN or Estradiol (E2) containing diet for 3 months. Methods: Ovariectomized (ovx) mice (n= 10/group) were fed with GEN containing pellets (0.01; 0.03; 0.1; 0.3; 1; 3 and 10 gram per kg diet). Control animals received either GEN free diet or E2 (4.3mg/kg diet). Animals were sacrificed after 3 months treatment and blood, uterus, liver and heart were collected, weighed and stored frozen for subsequent RT-PCR analysis. A mid left ventricle cross-sectional ring was collected for histological analysis. Results: The decrease of heart weight (HW) induced by ovariectomy (about 30% compared to intact mice) could be completely prevented by the doses of 3 and 10 g GEN/kg diet and by E2. Cardiomyocyte size was significantly increased by E2 but also by GEN at doses of 1, 3 and 10g/kg diet. In line with the increases of HW and cardiomyocyte size are changes of expression of marker genes of cardiac hypertrophy like IGF1, MHC, Actin 1 & 2 and Myocardin. Significant changes were observed with the doses of 1 g Gen/kg diet and higher. Expression of both ERs was not affected by GEN or E2. GEN induced also dose-dependent effects on expression of the known estrogen target gene IGF1 in uterus and liver. Conclusion: The GEN induced significant dose-dependent changes of HW, cardiomyocyte size and expression of marker genes of cardiac hypertrophy indicate direct action of this phytoestrogen on cardiomyoctye function.