The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor α AF-2 is modified
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- Sofia Movérare-Skrtic
- Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and
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- Anna E. Börjesson
- Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and
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- Helen H. Farman
- Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and
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- Klara Sjögren
- Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and
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- Sara H. Windahl
- Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and
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- Marie K. Lagerquist
- Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and
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- Annica Andersson
- Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and
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- Alexandra Stubelius
- Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and
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- Hans Carlsten
- Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and
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- Jan-Åke Gustafsson
- Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204
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- Claes Ohlsson
- Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and
書誌事項
- 公開日
- 2014-01-06
- DOI
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- 10.1073/pnas.1322910111
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:title>Significance</jats:title> <jats:p>Estrogen exerts important effects in the skeleton, which are primarily mediated via estrogen receptor (ER)α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. Previous studies demonstrate that ERα ligands might act as agonists, partial agonists, or antagonists. We demonstrate that the ERα antagonist ICI 182,780 (ICI) acts in a tissue-dependent manner in mice lacking ERαAF-2, resulting in no effect, agonistic activity, or inverse agonistic activity. Importantly, ICI exerted a pronounced inverse agonistic activity in the growth plate of mice lacking ERαAF-2. We propose that ERα lacking AF-2 is constitutively active in the absence of ligand in the growth plate, enabling ICI to act as an inverse agonist.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 111 (3), 1180-1185, 2014-01-06
Proceedings of the National Academy of Sciences
