{'fraction_non_alphanumeric': 0.02956989247311828, 'fraction_numerical': 0.016666666666666666, 'mean_word_length': 5.162251655629139, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Resveratrol Acts as a Mixed Agonist/Antagonist for Estrogen Receptors α and β.

Epidemiological evidence indicates that phytoestrogens inhibit cancer formation and growth, reduce cholesterol levels, and show benefits in treating osteoporosis. At least some of these activities are mediated through the interaction of phytoestrogens with estrogen receptors a and b (ERa and ERb). Resveratrol, trans-3,5,49-trihydroxystilbene, is a phytoestrogen in grapes that is present in red wine. Resveratrol was shown to bind ER in cytosolic extracts from MCF-7 and rat uteri. However, the contribution of ERa vs. ERb in this binding is unknown. Here we report that resveratrol binds ERb and ERa with comparable affinity, but with 7,000-fold lower affinity than estradiol (E2). Thus, resveratrol differs from other phytoestrogens that bind ERb with higher affinity than ERa. Resveratrol acts as an estrogen agonist and stimulates ERE-driven reporter gene activity in CHO-K1 cells expressing either ERa or ERb. The estrogen agonist activity of resveratrol depends on the ERE sequence and the type of ER. Resveratrol-liganded ERb has higher transcriptional activity than E2-liganded ERb at a single palindromic ERE. This indicates that those tissues that uniquely express ERb or that express higher levels of ERb than ERa may be more sensitive to resveratrol’s estrogen agonist activity. For the natural, imperfect EREs from the human c-fos, pS2, and progesterone receptor (PR) genes, resveratrol shows activity comparable to that induced by E2. We report that resveratrol exhibits E2 antagonist activity for ERa with select EREs. In contrast, resveratrol shows no E2 antagonist activity with ERb. These data indicate that resveratrol differentially affects the transcriptional activity of ERa and ERb in an ERE sequence-dependent manner. (Endocrinology 141: 3657‐3667, 2000)