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Altered ion transport by thyroid epithelia from CFTR −/− pigs suggests mechanisms for hypothyroidism in cystic fibrosis
Author(s) -
Li Hui,
Ganta Suhasini,
Fong Peying
Publication year - 2010
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2010.054700
Subject(s) - cystic fibrosis transmembrane conductance regulator , epithelial sodium channel , cystic fibrosis , endocrinology , medicine , thyroid , pendrin , amiloride , chemistry , apical membrane , secretion , ion transporter , chloride channel , epithelium , biology , sodium , transporter , biochemistry , pathology , organic chemistry , membrane , gene
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.