Two subtypes of estrogen receptors (ERs) have been identified in mammals: ERα and ERβ. Because effective antibodies against ERα proteins are available, expression and localization profiles of ERα proteins have been fully determined. By contrast, the paucity of well-validated antibodies against ERβ proteins has caused confusion regarding their expression and localization profiles, which has severely hindered the progress of ERβ research. Notably, the recent discovery of a monoclonal antibody (PPZ0506) specific for human ERβ proteins and its cross-reactivity to rat and mouse ERβ proteins has stimulated development of ERβ detection systems and the use of these systems to analyze the true localization profiles of ERβ proteins. In our previous studies, we reported the development and optimization of immunohistochemical staining methods for rat and mouse ERβ proteins with PPZ0506. Our immunohistochemical results revealed that rat and mouse ERβ proteins are expressed only in more localized tissues and cells than previously assumed, and further indicated that considerable species differences exist in ERβ expression among humans, rats, and mice. In the present review, we discuss various problems in previous ERβ research, new findings obtained using the PPZ0506 antibody, and prospects for future ERβ research.
