{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1362262944403774208.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.1322910111"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.1322910111"}}],"dc:title":[{"@value":"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"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Significance</jats:title>\n          <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>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380298343380160642","@type":"Researcher","foaf:name":[{"@value":"Sofia Movérare-Skrtic"}],"jpcoar:affiliationName":[{"@value":"Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380298343380160645","@type":"Researcher","foaf:name":[{"@value":"Anna E. Börjesson"}],"jpcoar:affiliationName":[{"@value":"Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380298343380160643","@type":"Researcher","foaf:name":[{"@value":"Helen H. Farman"}],"jpcoar:affiliationName":[{"@value":"Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380298343380160647","@type":"Researcher","foaf:name":[{"@value":"Klara Sjögren"}],"jpcoar:affiliationName":[{"@value":"Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380298343380160644","@type":"Researcher","foaf:name":[{"@value":"Sara H. Windahl"}],"jpcoar:affiliationName":[{"@value":"Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380298343380160648","@type":"Researcher","foaf:name":[{"@value":"Marie K. Lagerquist"}],"jpcoar:affiliationName":[{"@value":"Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380298343380160640","@type":"Researcher","foaf:name":[{"@value":"Annica Andersson"}],"jpcoar:affiliationName":[{"@value":"Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380298343380160646","@type":"Researcher","foaf:name":[{"@value":"Alexandra Stubelius"}],"jpcoar:affiliationName":[{"@value":"Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380298343380160649","@type":"Researcher","foaf:name":[{"@value":"Hans Carlsten"}],"jpcoar:affiliationName":[{"@value":"Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380298343380160641","@type":"Researcher","foaf:name":[{"@value":"Jan-Åke Gustafsson"}],"jpcoar:affiliationName":[{"@value":"Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204"}]},{"@id":"https://cir.nii.ac.jp/crid/1380298343380160650","@type":"Researcher","foaf:name":[{"@value":"Claes Ohlsson"}],"jpcoar:affiliationName":[{"@value":"Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden; and"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"2014-01-06","prism:volume":"111","prism:number":"3","prism:startingPage":"1180","prism:endingPage":"1185"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.1322910111"}],"createdAt":"2014-01-07","modifiedAt":"2022-04-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/2050588892096568704","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Construction of reporter gene assays using CWP and PDR mutant yeasts for enhanced detection of various sex steroids"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1073/pnas.1322910111"},{"@type":"CROSSREF","@value":"10.1186/s41021-020-00159-x_references_DOI_RTFDUoT0aooUkraSmSGamG5XLbB"}]}