Estrogen receptor beta: Tissue distribution and the still largely enigmatic physiological function

• The functions of ERβ in normal, healthy tissue are still largely unknown.
• The significance of ERβ mediated signaling in selected organs is reviewed.
• ERβ is a dominant-negative regulator of ERα mediated estrogen actions.

In 1996, the molecular biology of E2 had to be reevaluated: in an effort to identify novel nuclear receptors or unknown isoforms of existing receptors Kuiper and colleague described the expression of a novel subtype of the estrogen receptor (ER) in rat prostate and ovary. Upon this pioneering discovery the already known ER was renamed ERα while the newly described ER was termed ERβ. In this review an attempt is made to summarize the current knowledge regarding the expression and function of ERβ in selected reproductive and non-reproductive organs under physiological conditions. The data suggest that ERβ may be considered as a dominant-negative regulator of ERα modulating transcriptional responses to estrogens. The ratio of ER α vs. β. within a cell may determine the cell sensitivity to estrogens and its biological responses to the hormone. Conclusion: It is not the ligand, it is the multiplicity of receptors which determines the plethora of estrogen actions.This article is part of a Special Issue entitled ‘Phytoestrogens’.