Steroids and the endometrium

Steroids are commonly employed in current clinical practice. The benefits o f steroids in hormone replacement therapy, contraception and prevention or treatment of breast cancer are limited by their side effects arising from d isorders in endometrial function. These side effects are complex and enclos e bleeding problems and endometrial proliferation during hormone replacemen t therapy and antioestrogen treatment or menstrual disturbances during oral contraception. Numerous reports have identified gene targets influenced by steroids and ha ve implicated these products as contributors to endometrial physiology or p athology. The expression of estrogen and progesterone receptors is regulate d by steroids. The new estrogen receptor (ER) subtype ERP with different fu nctional characteristics from ER alpha was recently described in endometriu m. In addition, there is now increasing evidence that the functionally dist inct progesterone receptor (PR) isoforms A and B are differentially express ed in this tissue. The relative proportions of these steroid receptors and their interaction determine the expression of specific genes upon steroidal stimulation. Steroids induce endometrial expression of various growth and angiogenic fac tors. Dysregulations of this steroid modulated expression is believed to be involved in the pathogenesis of many endometrial diseases. Irregular bleed ing induced by steroidal contraception, for example, is thought to involve aberrant endometrial vascular development and expression of angiogenic grow th factors. The antioestrogen tamoxifen induces growth factors like vascula r endothelial growth factor and adrenomedullin which may be key mediators o f endometrial neoplastic effects. This review describes recent advances regarding the mechanism of action of steroids on endometrium. The expression of oestrogen and progesterone recep tors as well as steroid hormone dependent growth factors and angiogenic mod ulators are going to be discussed.