Partial and weak oestrogenicity of the red wine constituent resveratrol: Consideration of its superagonist activity in MCF-7 cells and its suggested cardiovascular protective effects

It was recently reported that the red wine phytoestrogen resveratrol (RES) acts as a superagonist to oestrogen-responsive MCF-7 cells. This activity o f RES was speculated to be relevant to the 'French paradox' in which modera te red wine consumption is reported to yield cardiovascular health benefits to humans. We report here that RES binds to oestrogen receptors (ER) isola ted from rat uterus with an affinity similar to 5 orders of magnitude lower than does either the reference synthetic oestrogen diethylstilboestrol (DE S) or oestradiol (E-2), In comparison with E-2 or DES, RES is only a weak a nd partial agonist in a yeast hER-alpha transcription assay and in cos-l ce ll assays employing transient transfections of ER-alpha or ER-beta associat ed with two different ER-response elements. Resveratrol was also concluded to be inactive in immature rat uterotrophic assays conducted using three da ily administrations of 0.03-120 mg kg(-1)/day(-1) RES (administered by eith er oral gavage or subcutaneous injection). These data weaken the suggestion that the oestrogenicity of RES may account for the reported cardiovascular protective effects of red wine consumption, and they raise questions regar ding the extent to which oestrogenicity data derived for a chemical using M CF-7 cells (or any other single ill vitro assay) can be used to predict the hormonal effects likely to occur in animals or humans. (C) 1998 John Wiley & Sons, Ltd.