Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta.
Level 5 - mechanism / opinion, no new human data
In vitro bench study using cell culture and receptor binding assays without human subjects.
PubMed 11014220 · doi:10.1210/endo.141.10.7721
What was done
Researchers evaluated the binding affinity of resveratrol for estrogen receptor alpha (ERalpha) versus estrogen receptor beta (ERbeta). They also tested resveratrol's estrogen agonist and antagonist activities using estrogen response element (ERE)-driven reporter gene assays in CHO-K1 cells expressing either ERalpha or ERbeta, testing both a single palindromic ERE and natural imperfect EREs from human *c-fos*, *pS2*, and progesterone receptor (*PR*) genes.
What was found
Resveratrol bound ERalpha and ERbeta with comparable affinity, but with 7,000-fold lower affinity than 17beta-estradiol (E2). In transcriptional reporter assays, resveratrol stimulated ERE-driven activity via both receptor subtypes. At a single palindromic ERE, resveratrol-liganded ERbeta had higher transcriptional activity than E2-liganded ERbeta. For natural EREs (*c-fos*, *pS2*, and *PR*), resveratrol induced activity comparable to E2. Additionally, resveratrol exhibited E2 antagonist activity for ERalpha at select EREs, but showed no E2 antagonist activity with ERbeta. Specific numeric values for binding constants or dose-response parameters were not reported in the abstract.
Why it matters
This study establishes resveratrol as a mixed estrogen receptor agonist/antagonist that acts in a receptor- and promoter sequence-dependent manner, differentiating its binding profile from other phytoestrogens that preferentially bind ERbeta.
Limits
The study is entirely in vitro using transfected non-human cells (CHO-K1), meaning it does not account for human metabolism, bioavailability, tissue distribution, or in vivo physiological outcomes. Exact binding constants, concentrations tested, and quantitative effect sizes are omitted from the abstract.
Cited by
- contradicts Resveratrol acts as a selective agonist for estrogen receptor beta (ERβ).