Is resveratrol an estrogen agonist in growing rats?

Trans-3,4,5-trihydroxystilbene (resveratrol), a polyphenolic compound found in juice and wine from dark-skinned grape cultivars, was recently shown to bind to estrogen receptors in vitro, where it activated transcription of e strogen-responsive reporter genes. The purpose of this 6-day study in weanl ing rats was to determine the dose response (1, 4, 10, 40, and 100 mu g/day ) effects of orally administered resveratrol on estrogen target tissues. Th e solvent (10% ethanol), had no significant effect on any measurement or de rived value. 17 beta-Estradiol treatment (100 mu g/day) decreased the growt h rate, final body weight, serum cholesterol, and radial bone growth (perio steal bone formation and mineral apposition rates) at the tibia-fibula syno stosis. In the uterus, 17 beta-estradiol treatment increased wet weight, ep ithelial cell height, and steady state messenger RNA levels for insulin-lik e growth factor I. In contrast, resveratrol treatment had no significant ef fect on body weight, serum cholesterol, radial bone growth, epithelial cell height, or messenger RNA levels for insulin-like growth factor I. Resverat rol treatment resulted in slight increases in uterine wet weight, but signi ficance was achieved at the 10-mu g dose only. A second experiment was perf ormed to determine whether a high dose of resveratrol (1000 mu g/day) antag onizes the ability of estrogen to lower serum cholesterol. As was shown for the lower doses, resveratrol had no effect on body weight, uterine wet wei ght, uterine epithelial cell height, cortical bone histomorphometry, or ser um cholesterol. 17 beta-Estradiol significantly lowered serum cholesterol, and this response was antagonized by cotreatment with resveratrol. These in vivo results suggest, in contrast to Drier in vitro studies, that resverat rol has little or no estrogen agonism on reproductive and nonreproductive e strogen target tissues and may be an estrogen antagonist.