What pharmacologists can learn from recent advances in estrogen signalling.

The discovery of the second estrogen receptor (ER) in 1995 surprised many endocrinologists and resulted in some scepticism regarding its physiological importance. However, 8 years later, it is clear that the multiple actions of estrogen in the body are mediated by two receptors that, although similar, are distinct gene products with non-overlapping functions. This clear delineation of the functions of the two receptors in such a short time was made possible by the development of ER alpha and ER beta knockout mice. The distinct patterns of tissue distribution of these two receptors has heightened interest in novel estrogen targets in the body and has led to awareness of new sites for pharmacological intervention in diseases such as depression, prostate dysfunction, leukaemia, inflammatory bowel disease and colon cancer.