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Physiological Reviews, Vol. 81, No. 4, October 2001, pp. 1535-1565
Copyright ©2001 by the American Physiological Society
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 ER
and ER
. 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 ER 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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