Effects of the isoflavone genistein on cardiac gene expression in ovariectomized mice

Objectives

Instead of synthetic hormones phytoestrogens like the isoflavone genistein (Gen) are increasingly used to treat diseases related to low endogenous estradiol (E2) production. Despite the presence of both known types of estrogen receptors (ER) in the heart, little is known about putative actions of phytoestrogens in the heart. To assess effects of a long term treatment with Gen on cardiac expression of ERs and estrogen-regulated genes, ovariectomized mice were fed for 3 months with a Gen or E2-containing diet. Gene expression in the heart was determined by real time PCR. Serum concentrations of E2 and Gen were measure by radioimmunoassay or HPLC, respectively.

Results

Long term application of E2 or Gen via pelleted food resulted in physiological serum levels of both compounds. Surprisingly, neither E2 nor Gen affected expression of ERα or β in the heart. Expression of the structural protein actin alpha 2 was up-regulated by E2 (124% of control), but down-regulated by Gen (73%) while mRNA levels of IGF1 were significantly increased by both, E2 and Gen (167 and 153%, respectively). Only Gen affected cardiac expression of the arylhydrocarbon receptor (128%). All observed changes were significant at the level of p ≤0.05 as tested with ANOVA followed by Dunnett's test.

Conclusions

The present data are the first evidence of effects of phytoestrogens in the heart. Though phytoestrogens like Gen bind to ERs, their effects on cardiac gene expression is distinct from those of E2. (Supported by EU contract: LSHM-CT-2005–018833)