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Physiol. Rev. 81: 1535-1565, 2001;
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Physiological Reviews, Vol. 81, No. 4, October 2001, pp. 1535-1565
Copyright ©2001 by the American Physiological Society

Mechanisms of Estrogen Action

Stefan Nilsson, Sari Mäkelä, Eckardt Treuter, Michel Tujague, Jane Thomsen, Göran Andersson, Eva Enmark, Katarina Pettersson, Margaret Warner, and Jan-Åke Gustafsson

KaroBio AB and Departments of Biosciences and of Medical Nutrition, Karolinska Institute, NOVUM; Department of Pathology, Huddinge Hospital, Huddinge, Sweden; and Institute of Biomedicin Department of Anatomy, University of Turku, Turku, Finland

Nilsson, Stefan, Sari Mäkelä, Eckardt Treuter, Michel Tujague, Jane Thomsen, Göran Andersson, Eva Enmark, Katarina Pettersson, Margaret Warner, and Jan-Åke Gustafsson. Mechanisms of Estrogen Action. Physiol. Rev. 81: 1535-1565, 2001.Our appreciation of the physiological functions of estrogens and the mechanisms through which estrogens bring about these functions has changed during the past decade. Just as transgenic mice were produced in which estrogen receptors had been inactivated and we thought that we were about to understand 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 ERalpha and ERbeta . Transgenic mice in which each of the receptors or both the receptors are inactive have revealed a much broader role for estrogens in the body than was previously thought. This decade also saw the description of a male patient who had no functional ERalpha and whose continued bone growth clearly revealed an important function of estrogen in men. The importance of estrogen in both males and females was also demonstrated in the laboratory in transgenic mice in which the aromatase gene was inactivated. Finally, crystal structures of the estrogen receptors with agonists and antagonists have revealed much about how ligand binding influences receptor conformation and how this conformation influences interaction of the receptor with coactivators or corepressors and hence determines cellular response to ligands.




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