Differential Ligand Activation of Estrogen Receptors ERα and ERβ at AP1 Sites
Abstract
The transactivation properties of the two estrogen receptors, ERα and ERβ, were examined with different ligands in the context of an estrogen response element and an AP1 element. ERα and ERβ were shown to signal in opposite ways when complexed with the natural hormone estradiol from an AP1 site: with ERα, 17β-estradiol activated transcription, whereas with ERβ, 17β-estradiol inhibited transcription. Moreover, the antiestrogens tamoxifen, raloxifene, and Imperial Chemical Industries 164384 were potent transcriptional activators with ERβ at an AP1 site. Thus, the two ERs signal in different ways depending on ligand and response element. This suggests that ERα and ERβ may play different roles in gene regulation.
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Estrogen receptor-β inhibits and estrogen receptor-α stimulates AVP neuronal activity in the supraoptic nucleus.
“Estrogen receptor–β (ERβ) inhibits (11), and estrogen receptor–α (ERα) stimulates, AVP neuronal activity in the SON (20).”
From Sex Hormone Effects on Body Fluid Regulation (2008) · cites this paper as [20]
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- Authors
- Paech, K., Webb, P., Kuiper, G. G. J. M., Nilsson, S., Gustafsson, J.-Å., Kushner, P. J., & Scanlan, T. S.
- Affiliations
- University of California, San Francisco (US)
- K. Paech and T. S. Scanlan, Departments of Pharmaceutical Chemistry and Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143–0446, USA.
- Corresponding author
- Kushner, Peter J.
- Scanlan, Thomas S.
- Venue
- Science
- Published
- 1997-09-05
- Volume
- 277
- Issue
- 5331
- Pages
- 1508-1510
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W4212936275
- Cited by
- 1,861
- References
- 17
- Citations by year
- 2026: 14 · 2025: 9 · 2024: 11 · 2023: 20 · 2022: 18 · 2021: 31 · 2020: 27 · 2019: 29 · 2018: 28 · 2017: 33 · 2016: 32 · 2015: 39 · 2014: 39 · 2013: 38 · 2012: 40
- FWCI
- 62.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29gm050672-03)
- National Institute of General Medical Sciences (GM 50672)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- estrogen receptor alpha, estrogen receptor beta, ligand-dependent transactivation, estrogen response element, estradiol, antiestrogens, tamoxifen, raloxifene, transcriptional activation, transcriptional repression, gene expression regulation
- MeSH terms
- Animals, Breast Neoplasms, Cell Line, Diethylstilbestrol, Enhancer Elements, Genetic, Estradiol, Estrogen Antagonists, Estrogens, Female, HeLa Cells, Humans, Ligands, Piperidines, Receptors, Estrogen, Tamoxifen, Transfection, Tumor Cells, Cultured, Uterus, Transcriptional Activation, Transcription Factor AP-1, Raloxifene Hydrochloride, Estrogen Receptor alpha, Estrogen Receptor beta, Rats, Polyunsaturated Alkamides
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