Estrogen modulating effects of resveratrol in female rats

Objectives: This study investigates the estrogen-like effects of resveratrol (RES) in female rats. Materials and Methods: In this two-step study on estrogenlike activity of RES, immature female rats (21 days old) were used in the first step and pubertal female rats (28 days old) with primary ovarian failure (POF) induced by 4-vinylcyclohexene diepoxide (VCD) were used in the second step. Possible agonistic and/or antagonistic effects of RES were investigated by using several parameters including the ratios of uterine/body weights (UBW), uterine dry/wet weights (UDWW) and body weight increase (BW%), bone density measurement, serum estradiol and vitamin D levels and histological evaluation. Results: In immature rats, RES resulted in an increase in UBW equal to that produced by 17 alpha-ethinyl estradiol (17alphaEE). The minimum effective dose for RES was 10 mg/kg. This effect was not decreased by tamoxifen but was significantly antagonized by fulvestrant. Similarly, tamoxifen did not abolish the effects of RES completely in rats with POF. However, in rats with VCDinduced POF, tamoxifen resulted in lower UBW values and estradiol levels were significantly higher in 17alphaEE-treated, RES+tamoxifen-treated and 17 beta-estradiol (17betaE)-treated rats compared to control animals. Conclusion: The dose of RES may be important in terms of estrogenic activity and even RES may modulate the effects of estrogen. Keywords: Estrogen, Resveratrol, 4-vinylcyclohexene diepoxide, Primary ovarian failure