Excess iodide induces an acute inhibition of the sodium/iodide symporter in thyroid male rat cells by increasing reactive oxygen species

Na⁺/I^- symporter (NIS) mediates iodide (I^-) uptake in the thyroid gland, the first and rate-limiting step in the biosynthesis of the thyroid hormones. The expression and function of NIS in thyroid cells is mainly regulated by TSH and by the intracellular concentration of I^-. High doses of I^- for 1 or 2 days inhibit the synthesis of thyroid hormones, a process known as the Wolff-Chaikoff effect. The cellular mechanisms responsible for this physiological response are mediated in part by the inhibition of I^- uptake through a reduction of NIS expression. Here we show that inhibition of I^- uptake occurs as early as 2 hours or 5 hours after exposure to excess I^- in FRTL-5 cells and the rat thyroid gland, respectively. Inhibition of I^- uptake was not due to reduced NIS expression or altered localization in thyroid cells. We observed that incubation of FRTL-5 cells with excess I^- for 2 hours increased H₂O₂ generation. Furthermore, the inhibitory effect of excess I^- on NIS-mediated I^- transport could be recapitulated by H₂O₂ and reverted by reactive derived oxygen species scavengers. The data shown here support the notion that excess I^- inhibits NIS at the cell surface at early times by means of a posttranslational mechanism that involves reactive derived oxygen species.