Excess Iodide Induces an Acute Inhibition of the Sodium/Iodide Symporter in Thyroid Male Rat Cells by Increasing Reactive Oxygen Species

• Published in: Endocrinology (Philadelphia) 2015-04, Vol.156 (4), p.1540-1551
• Main Authors: Arriagada, Alejandro A, Albornoz, Eduardo, Opazo, Ma. Cecilia, Becerra, Alvaro, Vidal, Gonzalo, Fardella, Carlos, Michea, Luis, Carrasco, Nancy, Simon, Felipe, Elorza, Alvaro A, Bueno, Susan M, Kalergis, Alexis M, Riedel, Claudia A
• Format: Article
• Language: English
• Subjects: Animals; Biosynthesis; Cell surface; Cell Survival - drug effects; Cell Survival - physiology; Hormones; Human health and pathology; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Iodides; Iodides - pharmacology; Life Sciences; Localization; Male; Oxygen; Physiological effects; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; Sodium; Sodium iodide symporter; Symporters - metabolism; Thyroid; Thyroid gland; Thyroid Gland - cytology; Thyroid Gland - drug effects; Thyroid Gland - metabolism; Thyroid hormones; Thyroid-stimulating hormone; Thyroid-TRH-TSH
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2014-1371

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.