Regulation of thyroid sodium‐iodide symporter in different stages of goiter: Possible involvement of reactive oxygen species

Abstract

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 H O generation in R1d-21d. Finally, we evaluated the effect of H O 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.

Bisphenol A increases hydrogen peroxide generation by thyrocytes both in vivo and in vitro

“…NIS has been shown to be sensitive to ROS ( 57 , 58 , 59 ). Since BPA induced an increment in H 2 O 2 generation, we have also evaluated NIS-mediated thyroid iodide uptake.…”

Painless thyroiditis mimicking relapse of hyperthyroidism during or after potassium iodide or thionamide therapy for Graves’ disease resulting in remission

“…1 and 2). Autoregulatory mechanisms in the thyroid gland are well known, and thyroid hormone synthesis was thought to be regulated by organified iodine compound X, probably an iodoaldehyde and/or iodolactone, which requires active thyroid peroxidase (TPO) to be synthesized, although the mechanisms underlying the effects of compound X remain elusive [38]. It is therefore plausible that a decreased ATD dosage might increase TPO activity and thereby increase the production of compound X, which suppresses the thyroid function, including that of sodium-iodide symporter (NIS), resulting in a decreased iodine uptake possibly accompanying Tg proteolysis and thyroid hormone release.…”

Bisphenols as Environmental Triggers of Thyroid Dysfunction: Clues and Evidence

“…Moreover, in female adult rats BPA lowered thyroid iodide uptake and thyroid peroxidase (TPO) activity, which are two essential steps in TH biosynthesis, probably due to an elevation of reactive oxygen species (ROS) production. Both NIS and TPO have been found to be sensitive to ROS [119,120], and in particular the decrease in TPO activity could be attributable to the oxidation of this enzyme [106]. Increased expression of pituitary Tshβ was reported in female rat neonates exposed to BPA [117], whereas Silva et al did not find any significant reduction of Tshβ mRNA levels in treated female rats [106].…”