Rapid regulation of thyroid sodium–iodide symporter activity by thyrotrophin and iodine

Abstract

Transport of iodide into thyrocytes, a fundamental step in thyroid hormone biosynthesis, depends on the presence of the sodium-iodide symporter (NIS). The importance of the NIS for diagnosis and treatment of diseases has raised several questions about its physiological control. The goal of this study was to evaluate the influence of thyroid iodine content on NIS regulation by thyrotrophin (TSH) in vivo. We showed that 15-min thyroid radioiodine uptake can be a reliable measurement of NIS activity in vivo. The effect of TSH on the NIS was evaluated in rats treated with 1-methyl-2-mercaptoimidazole (MMI; hypothyroid with high serum TSH concentrations) for 21 days, and after 1 (R1d), 2 (R2d), or 5 (R5d) days of withdrawal of MMI. NIS activity was significantly greater in both MMI and R1d rats. In R2d and R5d groups, thyroid iodide uptake returned to normal values, despite continuing high serum TSH, possibly as a result of the re-establishment of iodine organification after withdrawal of MMI. Excess iodine (0·05% NaI for 6 days) promoted a significant reduction in thyroid radioiodide uptake, an effect that was blocked by concomitant administration of MMI, confirming previous findings that iodine organification is essential for the iodide transport blockade seen during iodine overload. Therefore, our data show that modulation of the thyroid NIS by TSH depends primarily on thyroid iodine content and, further, that the regulation of NIS activity is rapid.

The importance of sodium/iodide symporter (NIS) for thyroid cancer management

“…The lower NIS activity in the presence of still elevated serum TSH indicates that organified iodine might be a potent NIS regulator, since 2 days after MMI withdrawal TPO has resumed its activity, leading to the production of an iodinated compound (IX), which might be responsible for the inhibition of iodide transport through the basolateral membrane of the thyrocyte. Serum T 4 also began to rise 2 days after MMI withdrawal, and reached normal values after 5 days without MMI, confirming the early TPO activity resumption after MMI withdrawal (26).…”

“…The latter being a pool of NIS protein that could be rapidly mobilized by TSH and other still undefined mechanisms (14,23,25). Recently, we have demonstrated the rapid modulation of NIS function at the plasma membrane using a new methodological approach in vivo (26): the precocious thyroid radioiodide uptake measurement (15 minutes after radioiodide administration). Some factors are determinants of iodine content in the thyroid gland: iodide uptake through NIS, iodide efflux and iodine organification at the apical membrane.…”

“…On the other hand, the 2h-iodide uptake is decreased by almost 90% when MMI is administered before iodide, showing that after 2 h of iodide administration the majority of iodide accumulated in the thyroid has already been organified. Thus, radioiodine content measured after 15 min of iodide administration can be an efficient evaluation of the basolateral transport of iodide through NIS, without the interference of iodide efflux and organification (26).…”

“…More recently, we showed that iodine excess also interferes with NIS function at the plasma membrane, since sodium iodide (NaI) administration for 6 days led to a significant reduction in NIS activity in vivo (26). NaI treatment is unable to reduce radioiodide transport when TPO activity was concomitantly inhibited by MMI administration, showing that NIS function is reduced by iodide only when TPO activity is present.…”

The effect of acute exercise session on thyroid hormone economy in rats

“…We have previously demonstrated that the measurement of radioiodide uptake 15 min after 125 I-NaI administration (short-term iodide uptake) reflects iodide transport through the NIS without the influence of in vivo thyroid iodine organification activity (Ferreira et al 2005). Thus, in order to evaluate the in vivo NIS function using thyroid radioiodine uptake measurements without the influence of the TPO iodine organification reaction, the animals received Na-125 I (250 000 c.p.m., i.p., Amersham) 15 min before decapitation.…”