{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:18:47Z","timestamp":1790759927779,"version":"4.1.0"},"reference-count":58,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T00:00:00Z","timestamp":1702944000000},"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":[[2024,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Tanycytes are specialized glial cells within the mediobasal hypothalamus that have multiple functions, including hormone sensing and regulation of hypophysiotropic hormone secretion. There are ongoing discussions about the role of tanycytes in regulating the supply of hypothalamic thyroid hormones (THs) through the expression of TH transporters (\n                      <jats:italic toggle=\"yes\">Slc16a2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Slco1c1<\/jats:italic>\n                      ) and deiodinases (\n                      <jats:italic toggle=\"yes\">Dio2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Dio3<\/jats:italic>\n                      ). In this study, we investigated the potential feedback effect of thyrotropin (TSH) on the transcription of these gatekeeper genes on tanycytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We analyzed the changes in the expression of TH-gatekeeper genes, in TSH-stimulated primary tanycytes, using quantitative polymerase chain reaction (qPCR). We also used RNAScope\n                      <jats:sup>\u00ae<\/jats:sup>\n                      in brain slices to further reveal the local distribution of the transcripts. In addition, we blocked intracellular pathways and used small-interfering RNA (siRNA) to elucidate differences in the regulation of the gatekeeper genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      TSH elevated messenger RNA (mRNA) levels of\n                      <jats:italic toggle=\"yes\">Slco1c1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Dio2<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Dio3<\/jats:italic>\n                      in tanycytes, while\n                      <jats:italic toggle=\"yes\">Slc16a2<\/jats:italic>\n                      was mostly unaffected. Blockade and knockdown of the TSH receptor (TSHR) and antagonization of cAMP response element-binding protein (CREB) clearly abolished the increased expression induced by TSH, indicating PKA-dependent regulation through the TSHR. The TSH-dependent expression of\n                      <jats:italic toggle=\"yes\">Dio3<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Slco1c1<\/jats:italic>\n                      was also regulated by protein kinase C (PKC), and in case of\n                      <jats:italic toggle=\"yes\">Dio3<\/jats:italic>\n                      , also by extracellular signal-regulated kinase (ERK) activity. Importantly, these gene regulations were specifically found in different subpopulations of tanycytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This study demonstrates that TSH induces transcriptional regulation of TH-gatekeeper genes in tanycytes through the Tshr\/G\u03b1q\/PKC pathway, in parallel to the Tshr\/G\u03b1s\/PKA\/CREB pathway. These differential actions of TSH on tanycytic subpopulations appear to be important for coordinating the supply of TH to the hypothalamus and aid its functions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2023.0375","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T01:58:51Z","timestamp":1703037531000},"page":"261-273","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["Regulation of Thyroid Hormone Gatekeepers by Thyrotropin in Tanycytes"],"prefix":"10.1177","volume":"34","author":[{"given":"Akila","family":"Chandrasekar","sequence":"first","affiliation":[{"name":"Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula Marie","family":"Schmidtlein","sequence":"additional","affiliation":[{"name":"Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Neve","sequence":"additional","affiliation":[{"name":"Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Rivagorda","sequence":"additional","affiliation":[{"name":"Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Spiecker","sequence":"additional","affiliation":[{"name":"Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Gauthier","sequence":"additional","affiliation":[{"name":"ENS de Lyon, INRAE, CNRS, Institut de G\u00e9nomique Fonctionnelle de Lyon, University of Lyon, Lyon, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Prevot","sequence":"additional","affiliation":[{"name":"Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience &amp; Cognition, UMR-S 1172, European Genomic Institute for Diabetes (EGID), University of Lille, Lille, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Schwaninger","sequence":"additional","affiliation":[{"name":"Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of L\u00fcbeck, L\u00fcbeck, Germany."},{"name":"DZHK (German Research Centre for Cardiovascular Research), Hamburg-L\u00fcbeck-Kiel, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2815-4426","authenticated-orcid":false,"given":"Helge","family":"M\u00fcller-Fielitz","sequence":"additional","affiliation":[{"name":"Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of L\u00fcbeck, L\u00fcbeck, 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