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Science 5 September 1997:
Vol. 277. no. 5331, pp. 1508 - 1510
DOI: 10.1126/science.277.5331.1508
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Reports

Differential Ligand Activation of Estrogen Receptors ERalpha and ERbeta at AP1 Sites

Kolja Paech, Paul Webb, George G. J. M. Kuiper, Stefan Nilsson, Jan-Åke Gustafsson, Peter J. Kushner, * Thomas S. Scanlan *

The transactivation properties of the two estrogen receptors, ERalpha and ERbeta , were examined with different ligands in the context of an estrogen response element and an AP1 element. ERalpha and ERbeta were shown to signal in opposite ways when complexed with the natural hormone estradiol from an AP1 site: with ERalpha , 17beta -estradiol activated transcription, whereas with ERbeta , 17beta -estradiol inhibited transcription. Moreover, the antiestrogens tamoxifen, raloxifene, and Imperial Chemical Industries 164384 were potent transcriptional activators with ERbeta at an AP1 site. Thus, the two ERs signal in different ways depending on ligand and response element. This suggests that ERalpha and ERbeta may play different roles in gene regulation.

K. Paech and T. S. Scanlan, Departments of Pharmaceutical Chemistry and Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143-0446, USA.
P. Webb and P. J. Kushner, Metabolic Research Unit, University of California, San Francisco, CA 94143-0540, USA.
G. G. J. M. Kuiper, Center for Biotechnology, Karolinska Institute, Novum, S-14186 Huddinge, Sweden.
S. Nilsson, Karo Bio AB, Novum, S-14157 Huddinge, Sweden.
J.-Å. Gustafsson, Center for Biotechnology and Department of Medical Nutrition, Karolinska Institute, Novum, S-14186 Huddinge, Sweden.
*   To whom correspondence should be addressed.

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Estrogenic Activities in Rodent Estrogen-Free Diets.
P. Ciana, A. Brena, P. Sparaciari, E. Bonetti, D. Di Lorenzo, and A. Maggi (2005)
Endocrinology 146, 5144-5150
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IL-1{beta}-Mediated Proinflammatory Responses Are Inhibited by Estradiol via Down-Regulation of IL-1 Receptor Type I in Uterine Epithelial Cells.
T. M Schaefer, J. A. Wright, P. A. Pioli, and C. R. Wira (2005)
J. Immunol. 175, 6509-6516
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Estrogen Receptor beta in Health and Disease.
O. Imamov, G.-J. Shim, M. Warner, and J.-A. Gustafsson (2005)
Biol Reprod 73, 866-871
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