RESVERATROL, A POLYPHENOLIC COMPOUND FOUND IN GRAPES AND WINE, IS AN AGONIST FOR THE ESTROGEN-RECEPTOR

The phytochemical resveratrol, which is found in grapes and wine, has been reported to have a variety of anti-inflammatory, anti-platelet, a nd anticarcinogenic effects. Based on its structural similarity to die thylstilbestrol, a synthetic estrogen, we examined whether resveratrol might be a phytoestrogen, At concentrations (approximate to 3-10 mu M ) comparable to those required for its other biological effects, resve ratrol inhibited the binding of labeled estradiol to the estrogen rece ptor and it activated transcription of estrogen-responsive reporter ge nes transfected into human breast cancer cells. This transcriptional a ctivation was estrogen receptor-dependent, required an estrogen respon se element in the reporter gene, and was inhibited by specific estroge n antagonists. In some cell types (e.g., MCF-7 cells), resveratrol fun ctioned as Ii superagonist (i.e., produced a greater maximal transcrip tional response than estradiol) whereas in others it produced activati on equal to or less than that of estradiol, Resveratrol also increased the expression of native estrogen-regulated genes, and it stimulated the proliferation of estrogen-dependent T47D breast cancer cells. Wt c onclude that resveratrol is a phytoestrogen and that it exhibits varia ble degrees of estrogen receptor agonism in different test. systems. T he estrogenic actions of resveratrol broaden the spectrum of its biolo gical actions and may be relevant to the reported cardiovascular benef its of drinking wine.