The discovery of a second estrogen receptor (ER), ERβ, has led to a complete change in our views on estrogen action. The previous dogmatic view that ERα represented the only estrogen receptor led to a static and simplistic concept of mechanisms of estrogen action with conceptual limitations in the development of novel estrogenic and antiestrogenic drugs. It is now realized that estrogen signaling represents a complex and multi facetted signal transduction pathway with, at least in many cases, quite different roles of ERα and ERβ. For instance, the two receptors appear to behave quite differently on AP1, antioxidant and Sp1-response elements where ERβ mediates positive regulation by antiestrogens whereas ERα is silent under these conditions. ERα and ERβ also appear to be differentially distributed in the body and within tissues. They are regulated differently and seem to have distinct biological roles, at least in certain contexts. Data are currently rapidly generated with respect to these issues from knockout animals with either of the two receptors deleted. Also double knockouts have been generated and apparently survive. ERβ may well have significant roles in the etiology of the following diseases and symptoms: prostate cancer, osteoporosis, depression, as well as urinary incontinence in postmenopausal women. Attempts are ongoing in several labs to develop specific ligands to the two receptors. Such ligands may well turn out to be extremely important in treating the mentioned diseases and symptoms as well as possibly others. Copyright (C) 2000 by W.B. Saunders Company.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Obstetrics and Gynecology