ECE2006 Poster Presentations Thyroid (174 abstracts)
ClC-5 does not affect megalin expression and function in the thyroid gland
S Lisi 1 , T Maritzen 2 , R Botta 1 , A Pinchera 1 , C Marcocci 1 , TJ Jentsch 2 & M Marinò 1
1Department of Endocrinology, University of Pisa, Pisa, Italy; 2Molecular Biology Center, University of Hamburg, Hamburg, Germany.
Megalin is a member of the LDL receptor family expressed by several epithelial cells where it mediates endocytosis of ligands. In the thyroid megalin is responsible for transcytosis of hormone-poor thyroglobulin (Tg) molecules. This process favors hormone release by preventing hormone-poor Tg to enter the lysosomal pathway, where hormones are cleaved from hormone-rich Tg molecules. Accordingly, megalin KO mice have a distinct thyroid phenotype with primary hypothyroidism. In renal proximal tubule cells megalin expression and function are reduced when the gene encoding ClC-5 is deleted or mutated. Here we investigated whether disruption of ClC-5 affects megalin expression and function also in the thyroid gland. For this purpose, we used the model of ClC-5 KO mice. By Western blotting of tissue extracts, ClC-5 was found to be expressed in the thyroid of WT mice, but not of ClC-5 KO mice. No differences were found in thyroid size, weight or histology between ClC-5 KO and WT mice. Expression of megalin, as detected by Western blotting in thyroid extracts, did not differ between ClC-5 KO and WT mice. In addition, serum levels of Tg, used as a measure of megalin-mediated transcytosis, were similar in the two groups of mice, suggesting that megalin function was unaffected by ClC-5 deficiency. Accordingly, serum levels of FT4 and TSH, unlike in megalin KO mice, were similar in ClC-5 KO and WT mice. Therefore, we concluded that, unlike in the kidney, ClC-5 does not affect megalin expression and function in thyroid epithelial cells, suggesting that expression of megalin undergoes different pathways of regulation in the two organs.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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