{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:25:45Z","timestamp":1783488345978,"version":"3.55.0"},"reference-count":42,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Stimulation of ventricular hypertrophy and heart rate are two major cardiac effects of thyroid hormone (TH). The aim of this study was to determine\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      which TH receptor (TR)\u2014\u03b1 or \u03b2\u2014and which mode of TR action\u2014canonical gene expression or DNA-binding independent noncanonical action\u2014mediate these effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We compared global TR\u03b1 and TR\u03b2 knockout mice (TR\u03b1\n                      <jats:sup>KO<\/jats:sup>\n                      ; TR\u03b2\n                      <jats:sup>KO<\/jats:sup>\n                      ) with wild-type (WT) mice to determine the TR isoform responsible for T3 effects. The relevance of TR DNA binding was studied in mice with a mutation in the DNA-binding domain that selectively abrogates DNA binding and canonical TR action (TR\u03b1\n                      <jats:sup>GS<\/jats:sup>\n                      ; TR\u03b2\n                      <jats:sup>GS<\/jats:sup>\n                      ). Hearts were studied with echocardiography at baseline and after 7 weeks of T3 treatment. Gene expression was measured with real-time polymerase chain reaction. Heart rate was recorded with radiotelemetry transmitters for 7 weeks in untreated, hypothyroid, and T3-treated mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      T3 induced ventricular hypertrophy in WT and TR\u03b2\n                      <jats:sup>KO<\/jats:sup>\n                      mice, but not in TR\u03b1\n                      <jats:sup>KO<\/jats:sup>\n                      mice. Hypertrophy was also induced in TR\u03b1\n                      <jats:sup>GS<\/jats:sup>\n                      mice. Thus, hypertrophy is mostly mediated by noncanonical TR\u03b1 action. Similarly, repression of\n                      <jats:italic toggle=\"yes\">Mhy7<\/jats:italic>\n                      occurred in WT and TR\u03b1\n                      <jats:sup>GS<\/jats:sup>\n                      mice. Basal heart rate was largely dependent on canonical TR\u03b1 action. But responsiveness to hypothyroidism and T3 treatment as well as expression of pacemaker gene\n                      <jats:italic toggle=\"yes\">Hcn2<\/jats:italic>\n                      were still preserved in TR\u03b1\n                      <jats:sup>KO<\/jats:sup>\n                      mice, demonstrating that TR\u03b2 could compensate for absence of TR\u03b1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>T3-induced cardiac hypertrophy could be attributed to noncanonical TR\u03b1 action, whereas heart rate regulation was mediated by canonical TR\u03b1 action. TR\u03b2 could substitute for canonical but not noncanonical TR\u03b1 action.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2023.0683","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T07:11:48Z","timestamp":1715929908000},"page":"785-795","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Canonical and Noncanonical Contribution of Thyroid Hormone Receptor Isoforms Alpha and Beta to Cardiac Hypertrophy and Heart Rate in Male Mice"],"prefix":"10.1177","volume":"34","author":[{"given":"Daniela","family":"Geist","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5080-7166","authenticated-orcid":false,"given":"Georg Sebastian","family":"H\u00f6nes","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne Camilla","family":"Grund","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janina","family":"Pape","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1869-1930","authenticated-orcid":false,"given":"Devon","family":"Siemes","sequence":"additional","affiliation":[{"name":"Department of Immunodynamics, Institute of Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa","family":"Spangenberg","sequence":"additional","affiliation":[{"name":"Department of Immunodynamics, Institute of Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elen","family":"Tolstik","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Pharmacology, Translational Research, Leibniz-Institut f\u00fcr Analytische Wissenschaften\u2014ISAS, Dortmund, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"D\u00f6rr","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Pharmacology, Translational Research, Leibniz-Institut f\u00fcr Analytische Wissenschaften\u2014ISAS, Dortmund, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Spielmann","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Gailus-Durner","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hrabe de Angelis","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany."},{"name":"German Center for Diabetes Research, Neuherberg, Germany."},{"name":"Chair of Experimental Genetics, School of Life Science Weihenstephan, Technische Universit\u00e4t M\u00fcnchen, Freising, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7778-5158","authenticated-orcid":false,"given":"Jens","family":"Mittag","sequence":"additional","affiliation":[{"name":"Center of Brain Behavior and Metabolism (CBBM), Institute for Endocrinology and Diabetes, University of L\u00fcbeck and Universit\u00e4tsklinikum Schleswig-Holstein Campus L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Robert","family":"Engel","sequence":"additional","affiliation":[{"name":"Department of Immunodynamics, Institute of Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"F\u00fchrer","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Pharmacology, Translational Research, Leibniz-Institut f\u00fcr Analytische Wissenschaften\u2014ISAS, Dortmund, Germany."},{"name":"Institute of Pharmacology and Toxicology, University of W\u00fcrzburg, W\u00fcrzburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9330-9036","authenticated-orcid":false,"given":"Lars Christian","family":"Moeller","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, 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