LAUSR

Na+/I− symporter (NIS) transports iodide into thyrocytes, a fundamental step for thyroid hormone biosynthesis. Our aim was to evaluate NIS regulation in different status of goitrogenesis and its underlying mechanisms. Wistar rats were treated with methimazole (MMI) for 5 and 21 days, to achieve different status of goiter. We then evaluated the effect of MMI removal for 1 day (R1d), after 5 (R1d‐5d) or 21 (R1d‐21d) days of MMI treatment. MMI increased thyroid weight, iodide uptake and in vitro TPO activity in a time‐dependent way. Although MMI removal evoked a rapid normalization of TPO activity in R1d‐5d, it was still high in R1d‐21d. On the other hand, iodide uptake was rapidly down‐regulated in R1d‐21d, but not in R1d‐5d, suggesting that the increased TPO activity in R1d‐21d led to increased intraglandular organified iodine (I‐X), which is known to inhibit iodide uptake. Since TGFβ has been shown to mediate some effects of I‐X, we evaluated TGFβ and TGFβ receptor mRNA levels, which were increased in R1d‐21d. Moreover, it has been demonstrated that TGFβ stimulates NOX4. Accordingly, our data revealed increased NOX4 expression and H2O2 generation in R1d‐21d. Finally, we evaluated the effect of H2O2 on NIS function and mRNA levels in PCCL3 thyroid cell line, which were reduced. Thus, the present study suggests that there is a relationship between the size of the goiter and NIS regulation and that the mechanism might involve I‐X, TGFβ, NOX4 and increased ROS production.