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• W1520708441 startingPage "1132" @default.
• W1520708441 abstract "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⁻ and absorbs Na(+) in response to cAMP. Chloride secretion may provide a counter-ion for the SLC26A4 (pendrin)-mediated I⁻ secretion which is required for the first step of thyroid hormonogenesis, thyroglobulin iodination. In contrast, few models exist to explain a role for Na(+) absorption. Whether CFTR mediates the secretory Cl⁻ current in thyroid epithelium has not been directly addressed. We used thyroids from a novel pig CFTR(-/-) model, generated primary pig thyroid epithelial cell cultures (pThECs), analysed these cultures for preservation of thyroid-specific transcripts and proteins, and monitored the following parameters: (1) the Cl⁻ secretory response to the cAMP agonist, isoprenaline; and (2) the amiloride-sensitive Na(+) current. Baseline short-circuit current (I(sc)) did not differ between CFTR(+/+) and CFTR(-/-) cultures. Serosal isoprenaline increased I(sc) in CFTR(+/+), but not CFTR(-/-), monolayers. Compared with CFTR(+/+) thyroid cultures, amiloride-sensitive Na(+) absorption measured in CFTR(-/-) pThECs represented a greater fraction of the resting I(sc). However, levels of transcripts encoding epithelial sodium channel (ENaC) subunits did not differ between CFTR(+/+) and CFTR(-/-) pThECs. Immunoblot analysis verified ENaC subunit protein expression, but quantification indicated no difference in expression levels. Our studies definitively demonstrate that CFTR mediates cAMP-stimulated Cl⁻ secretion in a well-differentiated thyroid culture model and that knockout of CFTR promotes increased Na(+) absorption by a mechanism other than increased ENaC expression. These findings suggest several models for the mechanism of cystic fibrosis-associated hypothyroidism." @default.
• W1520708441 created "2016-06-24" @default.
• W1520708441 creator A5036709058 @default.
• W1520708441 creator A5062168167 @default.
• W1520708441 creator A5073998098 @default.
• W1520708441 date "2010-09-20" @default.
• W1520708441 modified "2023-10-10" @default.
• W1520708441 title "Altered ion transport by thyroid epithelia from<i>CFTR</i>^−/−pigs suggests mechanisms for hypothyroidism in cystic fibrosis" @default.
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• W1520708441 doi "https://doi.org/10.1113/expphysiol.2010.054700" @default.
• W1520708441 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2991370" @default.
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