The Unexpected Science of Estrogen Receptor-β Selective Agonists: A New Class of Anti-Inflammatory Agents?

In the nine years since the unexpected discovery of a second form of the estrogen receptor (ER), ERbeta has been mentioned in about 2,800 literature citations. Such prolific research is testimony to interest in explaining its role in estrogen physiology as well as investigating its potential as a drug target. Our current understanding is that ERalpha, not ERbeta is responsible for mediating the effects of estrogens in "classic" model systems such as the reproductive tract and skeleton. The role of ERbeta is still being defined, but profiling of ERbeta selective agonists in several animal models of human disease indicates these compounds may have utility as novel anti-inflammatory agents. The challenge for the future is to elucidate their mechanism of action and determine the clinical relevance of the impressive preclinical observations.