Biological functions and clinical implications of oestrogen receptors alfa and beta in epithelial tissues

For the past 10 years it is known that oestrogen functions through the activation of two oestrogen receptors (ERalpha and ERbeta). To the great surprise of endocrinologists, ERbeta was found to be widely distributed in tissues throughout the body including tissues previously considered as 'oestrogen insensitive'. The epithelium of the ventral prostate and lung as well as ovarian granulosa cells are ERalpha-negative but ERbeta-positive and in these tissues ERbeta seems to be involved in important physiological processes, like differentiation, extracellular matrix organization and stromal-epithelial communication. In tissues where both ERs are expressed, the two receptors seem to counteract each other. In the uterus, mammary gland and immune system, ERalpha promotes proliferation whereas ERbeta has pro-apoptotic and pro-differentiating functions. The challenge of the future will be to develop specific agonists, which can selectively activate/inactivate either ERalpha or ERbeta. These pharmaceuticals are likely to be of clinical importance in the prevention or treatment of various diseases.