Abstract
Estrogen receptor β (ERβ) was discovered in 1995 and reported on in 1996. During the 10 years following this event, our understanding of estrogen signaling has changed remarkably. We now know that estradiol, the major endogenous activator of ER, is non-selective for the two receptors, and that ERα and ERβ are, in many contexts, antagonistic against one another, an example of a yin/yang relationship, perhaps nature's way to accomplish subtle regulatory changes of estrogen signaling as a response to ever-shifting physiological requirements. Needless to say, this knowledge is of paramount significance pharmaceutically, and several ERβ-selective agonists, intended for use against a multitude of diseases, have already been synthesized and patented by drug companies. Clearly, the next 5–10 years will be extremely exciting in view of results from clinical trials testing the clinical utility of ERβ targeted drugs.