{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:56:45Z","timestamp":1790488605912,"version":"4.1.0"},"reference-count":49,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T00:00:00Z","timestamp":1596240000000},"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":[[2020,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Tachycardia, cardiac hypertrophy, and elevated body temperature are major signs of systemic hyperthyroidism, which are considered to reflect the excessive thyroid hormone (TH) action in the respective peripheral tissues. However, recent observations indicate that the central actions of TH also contribute substantially to cardiovascular regulation and thermogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      In this study, we dissect the individual contributions of peripheral TH action versus the central effects in body temperature regulation and cardiovascular functions by taking advantage of mice lacking the TH transporters monocarboxylate transporter 8 (MCT8) and organic anion transporting polypeptide 1C1 (OATP1C1) (\n                      <jats:italic toggle=\"yes\">M\/O<\/jats:italic>\n                      double knock-out [dko]), which exhibit elevated serum triiodothyronine (T3) levels while their brain is in a profoundly hypothyroid state. We compared these animals with wild-type (WT) mice that were treated orally with T3 to achieve similarly elevated serum T3 levels, but are centrally hyperthyroid. For the studies, we used radiotelemetry, infrared thermography, gene expression profiling, Western blot analyses, and enzyme linked immunosorbent assays (ELISA) assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Our analyses revealed mild hyperthermia and cardiac hypertrophy in T3-treated WT mice but not in\n                      <jats:italic toggle=\"yes\">M\/O<\/jats:italic>\n                      dko animals, suggesting that central actions of TH are required for these hyperthyroid phenotypes. Although the average heart rate was unaffected in either model, the\n                      <jats:italic toggle=\"yes\">M\/O<\/jats:italic>\n                      dko exhibited an altered heart rate frequency distribution with tachycardic bursts in active periods and bradycardic episodes during resting time, demonstrating that the stabilization of heart rate by the autonomic nervous system can be impaired in centrally hypothyroid animals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our studies unravel distinct phenotypical traits of hyperthyroidism that depend on an intact central nervous system, and provide valuable insight into the cardiovascular pathology of the Allan\u2013Herndon\u2013Dudley syndrome, a condition caused by the lack of MCT8 in humans.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2019.0705","type":"journal-article","created":{"date-parts":[[2020,3,19]],"date-time":"2020-03-19T02:37:26Z","timestamp":1584585446000},"page":"1205-1216","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":22,"title":["Central Hypothyroidism Impairs Heart Rate Stability and Prevents Thyroid Hormone-Induced Cardiac Hypertrophy and Pyrexia"],"prefix":"10.1177","volume":"30","author":[{"given":"Beate","family":"Herrmann","sequence":"first","affiliation":[{"name":"Department of Molecular Endocrinology, Institute for Endocrinology and Diabetes, Center of Brain Behavior and Metabolism (CBBM), University of L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisbeth","family":"Harder","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, Institute for Endocrinology and Diabetes, Center of Brain Behavior and Metabolism (CBBM), University of L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Oelkrug","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, Institute for Endocrinology and Diabetes, Center of Brain Behavior and Metabolism (CBBM), University of L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiesi","family":"Chen","sequence":"additional","affiliation":[{"name":"Leibniz Research Institute for Environmental Medicine (IUF), D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sogol","family":"Gachkar","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, Institute for Endocrinology and Diabetes, Center of Brain Behavior and Metabolism (CBBM), University of L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Nock","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, Institute for Endocrinology and Diabetes, Center of Brain Behavior and Metabolism (CBBM), University of L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Resch","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, Institute for Endocrinology and Diabetes, Center of Brain Behavior and Metabolism (CBBM), University of L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Korkowski","sequence":"additional","affiliation":[{"name":"Leibniz Research Institute for Environmental Medicine (IUF), D\u00fcsseldorf, Germany."},{"name":"Department of Endocrinology, University Hospital Essen, University Duisburg-Essen, Essen, 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