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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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   Abstract »    Full Text »    PDF »
Coordinate Regulation of Neuropeptide Y and Agouti-Related Peptide Gene Expression by Estrogen Depends on the Ratio of Estrogen Receptor (ER) {alpha} to ER{beta} in Clonal Hypothalamic Neurons.
D. Titolo, F. Cai, and D. D. Belsham (2006)
Mol. Endocrinol. 20, 2080-2092
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Molecular Mechanism of Inhibitory Aryl Hydrocarbon Receptor--Estrogen Receptor/Sp1 Cross Talk in Breast Cancer Cells.
S. Khan, R. Barhoumi, R. Burghardt, S. Liu, K. Kim, and S. Safe (2006)
Mol. Endocrinol. 20, 2199-2214
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Effects of Hormone Replacement Therapy Type and Route of Administration on Plasma Matrix Metalloproteinases and Their Tissue Inhibitors in Postmenopausal Women.
K. C. Lewandowski, J. Komorowski, D. P. Mikhalidis, M. Bienkiewicz, B. K. Tan, C. J. O'Callaghan, A. Lewinski, G. Prelevic, and H. S. Randeva (2006)
J. Clin. Endocrinol. Metab. 91, 3123-3130
   Abstract »    Full Text »    PDF »
Estrogen synthesis in the spinal dorsal horn: a new central mechanism for the hormonal regulation of pain..
H. C. Evrard (2006)
Am J Physiol Regulatory Integrative Comp Physiol 291, R291-R299
   Abstract »    Full Text »    PDF »
Regional, Laminar and Cellular Distribution of Immunoreactivity for ER{beta} in the Cerebral Cortex of Hormonally Intact, Postnatally Developing Male and Female Rats.
M. F. Kritzer (2006)
Cereb Cortex 16, 1181-1192
   Abstract »    Full Text »    PDF »
Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome..
J. Frasor, E. C. Chang, B. Komm, C.-Y. Lin, V. B. Vega, E. T. Liu, L. D. Miller, J. Smeds, J. Bergh, and B. S. Katzenellenbogen (2006)
Cancer Res. 66, 7334-7340
   Abstract »    Full Text »    PDF »
A Novel Estradiol/Estrogen Receptor {alpha}-dependent Transcriptional Mechanism Controls Expression of the Human Prolactin Receptor.
J. Dong, C.-H. Tsai-Morris, and M. L. Dufau (2006)
J. Biol. Chem. 281, 18825-18836
   Abstract »    Full Text »    PDF »
Acetylation of Estrogen Receptor {alpha} by p300 at Lysines 266 and 268 Enhances the Deoxyribonucleic Acid Binding and Transactivation Activities of the Receptor.
M. Y. Kim, E. M. Woo, Y. T. E. Chong, D. R. Homenko, and W. L. Kraus (2006)
Mol. Endocrinol. 20, 1479-1493
   Abstract »    Full Text »    PDF »
Estrogenic effects of natural and synthetic compounds including tibolone assessed in Saccharomyces cerevisiae expressing the human estrogen {alpha} and {beta} receptors.
G. Hasenbrink, A. Sievernich, L. Wildt, J. Ludwig, and H. Lichtenberg-Frate (2006)
FASEB J 20, 1552-1554
   Abstract »    Full Text »    PDF »
Treatment with an estrogen receptor alpha ligand is neuroprotective in experimental autoimmune encephalomyelitis..
L. B. J. Morales, K. K. Loo, H.-b. Liu, C. Peterson, S. Tiwari-Woodruff, and R. R. Voskuhl (2006)
J. Neurosci. 26, 6823-6833
   Abstract »    Full Text »    PDF »
Gender Differences of Cardiovascular Disease: New Perspectives for Estrogen Receptor Signaling.
M. R. Meyer, E. Haas, and M. Barton (2006)
Hypertension 47, 1019-1026
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Ligand-Independent Effects of Estrogen Receptor {beta} on Mouse Gonadotropin-Releasing Hormone Promoter Activity.
T. R. Pak, W. C. J. Chung, J. L. Roberts, and R. J. Handa (2006)
Endocrinology 147, 1924-1931
   Abstract »    Full Text »    PDF »
Downregulation of Estrogen Receptor Gene Expression by Exogenous 17{beta}-Estradiol in the Mammary Glands of Lactating Mice..
T. Hatsumi and Y. Yamamuro (2006)
Experimental Biology and Medicine 231, 311-316
   Abstract »    Full Text »    PDF »
Estrogen Receptor (ER) {beta} Modulates ER{alpha}-Mediated Transcriptional Activation by Altering the Recruitment of c-Fos and c-Jun to Estrogen-Responsive Promoters.
J. Matthews, B. Wihlen, M. Tujague, J. Wan, A. Strom, and J.-A. Gustafsson (2006)
Mol. Endocrinol. 20, 534-543
   Abstract »    Full Text »    PDF »
3-Methylcholanthrene and Other Aryl Hydrocarbon Receptor Agonists Directly Activate Estrogen Receptor {alpha}.
M. Abdelrahim, E. Ariazi, K. Kim, S. Khan, R. Barhoumi, R. Burghardt, S. Liu, D. Hill, R. Finnell, B. Wlodarczyk, et al. (2006)
Cancer Res. 66, 2459-2467
   Abstract »    Full Text »    PDF »
Evidence that the mouse insulin receptor substrate-1 belongs to the gene family on which the promoter is activated by estrogen receptor {alpha} through its interaction with Sp1.
M L Panno, L Mauro, S Marsico, D Bellizzi, P Rizza, C Morelli, M Salerno, F Giordano, and S Ando' (2006)
J. Mol. Endocrinol. 36, 91-105
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Gonadotropin-secreting cells in ovariectomized rats treated with different oestrogen receptor ligands: a modulatory role for ER{beta} in the gonadotrope?.
J E Sanchez-Criado, J M. de las Mulas, C Bellido, V M Navarro, R Aguilar, J C Garrido-Gracia, M M Malagon, M Tena-Sempere, and A Blanco (2006)
J. Endocrinol. 188, 167-177
   Abstract »    Full Text »    PDF »
Stimulation of the Novel Estrogen Receptor-{alpha} Intronic TERP-1 Promoter by Estrogens, Androgen, Pituitary Adenylate Cyclase-Activating Peptide, and Forskolin, and Autoregulation by TERP-1 Protein.
W. M. Bryant, M. A. Gibson, and M. A. Shupnik (2006)
Endocrinology 147, 543-551
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Stimulatory Cross-talk between NFAT3 and Estrogen Receptor in Breast Cancer Cells.
H. Zhang, X. Xie, X. Zhu, J. Zhu, C. Hao, Q. Lu, L. Ding, Y. Liu, L. Zhou, Y. Liu, et al. (2005)
J. Biol. Chem. 280, 43188-43197
   Abstract »    Full Text »    PDF »
Mechanisms of endocrine resistance and novel therapeutic strategies in breast cancer.
N. Normanno, M. Di Maio, E. De Maio, A. De Luca, A. de Matteis, A. Giordano, F. Perrone, and on behalf of the NCI-Naples Breast Cancer Group (2005)
Endocr. Relat. Cancer 12, 721-747
   Abstract »    Full Text »    PDF »
Coregulators in Nuclear Estrogen Receptor Action: From Concept to Therapeutic Targeting.
J. M. Hall and D. P. McDonnell (2005)
Mol. Interv. 5, 343-357
   Abstract »    Full Text »    PDF »
Recruitment of Histone Deacetylase 4 to the N-Terminal Region of Estrogen Receptor {alpha}.
H. Leong, J. R. Sloan, P. D. Nash, and G. L. Greene (2005)
Mol. Endocrinol. 19, 2930-2942
   Abstract »    Full Text »    PDF »


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