{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:57:04Z","timestamp":1791082624126,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2010,9,20]],"date-time":"2010-09-20T00:00:00Z","timestamp":1284940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:p><jats:bold>Subclinical hypothyroidism has been linked to cystic fibrosis, and the cystic fibrosis transmembrane conductance regulator (CFTR) shown to be expressed in the thyroid. The thyroid epithelium secretes Cl<jats:sup>\u2212<\/jats:sup> and absorbs Na<jats:sup>+<\/jats:sup> in response to cAMP. Chloride secretion may provide a counter\u2010ion for the SLC26A4 (pendrin)\u2010mediated I<jats:sup>\u2212<\/jats:sup> secretion which is required for the first step of thyroid hormonogenesis, thyroglobulin iodination. In contrast, few models exist to explain a role for Na<jats:sup>+<\/jats:sup> absorption. Whether CFTR mediates the secretory Cl<jats:sup>\u2212<\/jats:sup> current in thyroid epithelium has not been directly addressed. We used thyroids from a novel pig <jats:italic>CFTR<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> model, generated primary pig thyroid epithelial cell cultures (pThECs), analysed these cultures for preservation of thyroid\u2010specific transcripts and proteins, and monitored the following parameters: (1) the Cl<jats:sup>\u2212<\/jats:sup> secretory response to the cAMP agonist, isoprenaline; and (2) the amiloride\u2010sensitive Na<jats:sup>+<\/jats:sup> current. Baseline short\u2010circuit current (<jats:italic>I<\/jats:italic><jats:sub>sc<\/jats:sub>) did not differ between <jats:italic>CFTR<\/jats:italic><jats:sup>+\/+<\/jats:sup> and <jats:italic>CFTR<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> cultures. Serosal isoprenaline increased <jats:italic>I<\/jats:italic><jats:sub>sc<\/jats:sub> in <jats:italic>CFTR<\/jats:italic><jats:sup>+\/+<\/jats:sup>, but not <jats:italic>CFTR<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>, monolayers. Compared with <jats:italic>CFTR<\/jats:italic><jats:sup>+\/+<\/jats:sup> thyroid cultures, amiloride\u2010sensitive Na<jats:sup>+<\/jats:sup> absorption measured in <jats:italic>CFTR<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> pThECs represented a greater fraction of the resting <jats:italic>I<\/jats:italic><jats:sub>sc<\/jats:sub>. However, levels of transcripts encoding epithelial sodium channel (ENaC) subunits did not differ between <jats:italic>CFTR<\/jats:italic><jats:sup>+\/+<\/jats:sup> and <jats:italic>CFTR<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> pThECs. Immunoblot analysis verified ENaC subunit protein expression, but quantification indicated no difference in expression levels. Our studies definitively demonstrate that CFTR mediates cAMP\u2010stimulated Cl<jats:sup>\u2212<\/jats:sup> secretion in a well\u2010differentiated thyroid culture model and that knockout of <jats:italic>CFTR<\/jats:italic> promotes increased Na<jats:sup>+<\/jats:sup> absorption by a mechanism other than increased ENaC expression. These findings suggest several models for the mechanism of cystic fibrosis\u2010associated hypothyroidism.<\/jats:bold><\/jats:p>","DOI":"10.1113\/expphysiol.2010.054700","type":"journal-article","created":{"date-parts":[[2010,8,21]],"date-time":"2010-08-21T00:46:19Z","timestamp":1282351579000},"page":"1132-1144","source":"Crossref","is-referenced-by-count":43,"title":["Altered ion transport by thyroid epithelia from <i>CFTR<\/i><sup>\u2212\/\u2212<\/sup> pigs suggests mechanisms for hypothyroidism in cystic 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