Mechanisms of estrogen action

Our appreciation of the physiological functions of estrogens and the mechan isms through which estrogens bring about these functions has changed during the past decade. Just as transgenic mice were produced in which estrogen r eceptors had been inactivated and we thought that we were about to understa nd the role of estrogen receptors in physiology and pathology, it was found that there was not one but two distinct and functional estrogen receptors, now called Ella and ERP. Transgenic mice in which each of the receptors or both the receptors are inactive have revealed a much broader role for estr ogens in the body than was previously thought. This decade also saw the des cription of a male patient who had no functional ER alpha and whose continu ed bone growth clearly revealed an important function of estrogen in men. T he importance of estrogen in both males and females was also demonstrated i n the laboratory in transgenic mice in which the aromatase gene was inactiv ated. Finally, crystal structures of the estrogen receptors with agonists a nd antagonists have revealed much about how ligand binding influences recep tor conformation and how this conformation influences interaction of the re ceptor with coactivators or corepressors and hence determines cellular resp onse to ligands.