Abstract
About 50% of patients with Pendreds syndrome develop goiter and hypothyroidism with iodination defect, due to the lack of pendrin believed to transport iodide in colloid. The aim was to analyse if the lack of pendrin modifies 1° the expression of Dual oxidase (DUOX) generating H2O2 and thyroperoxydase (TPO), 2° cell structure. We performed a morphological analysis of thyroid samples from a Pendreds patient with goiter and from normal paranodular thyroids. Thyroglobulin (Tg), T4-rich Tg, T4, DUOX, TPO, Pendrin, 6-hydroxynonenal (HNE), activated caspase-6, Peroxiredoxin 5 (PRDX5) and catalase were detected by immunohistochemistry. The localization of 127Iodine was determined by ion imaging. There was a great heterogeneity between the different samples of the Pendreds thyroid. There were large zones of destroyed follicles and other zones with encapsulated clusters of follicles with a typical morphology. Their lumina were filled with thyroglobulin, but no T4-rich Tg nor T4 were detected suggesting a defect of iodination probably due to the lack of pendrin which was not detected at the apical pole of thyrocytes, at the opposite of “normal” cells. This was confirmed by ion imaging showing that organic 127I was not detected in some lumina, but well in the cytoplasm. In “cold” follicles of Pendreds thyroid, as compared to “normal” gland, the expression of DUOX and TPO was increased. DUOX and TPO were detected in the cytoplasm rather than at the apical pole. The Pendreds thyroid also presented thyrocytes alterations. This was demonstrated by increased expression of HNE, marker of lipid peroxidation, and of activated caspase-6, marker of apoptosis. However, the cells did develop protective defences, as shown by increased expression of PRDX5 and catalase, detoxifying H2O2.
In conclusion, pendrin lack impairs iodination, induces upregulation and mislocalization of DUOX and TPO. The excess of H2O2 not used for iodination, could provokes cell toxicity.