Departamento de Ciências Básicas, ISNF, Universidade Federal Fluminense, Nova Friburgo, RJ, Brazil.
Laboratório de Fisiologia Endócrina Doris Rosenthal, IBCCF, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Clin Exp Pharmacol Physiol. 2018 Apr;45(4):326-334. doi: 10.1111/1440-1681.12887. Epub 2017 Dec 19.
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.
钠/碘同向转运体（NIS）将碘转运入甲状腺细胞，这是甲状腺激素生物合成的基本步骤。我们的目的是评估不同甲状腺肿状态下 NIS 的调节及其潜在机制。Wistar 大鼠用甲巯咪唑（MMI）处理 5 和 21 天，以达到不同的甲状腺肿状态。然后，我们评估了 MMI 去除 1 天（R1d）、5 天（R1d-5d）或 21 天（R1d-21d）后的效果。MMI 以时间依赖性方式增加甲状腺重量、碘摄取和体外 TPO 活性。尽管 MMI 去除在 R1d-5d 时迅速使 TPO 活性正常化，但在 R1d-21d 时仍很高。另一方面，碘摄取在 R1d-21d 时迅速下调，但在 R1d-5d 时则不然，这表明 R1d-21d 中增加的 TPO 活性导致了细胞内有机碘（I-X）的增加，已知 I-X 会抑制碘摄取。由于 TGFβ 已被证明介导 I-X 的一些作用，我们评估了 TGFβ 和 TGFβ 受体 mRNA 水平，它们在 R1d-21d 中增加。此外，已经证明 TGFβ 刺激 NOX4。相应地，我们的数据显示 R1d-21d 中 NOX4 表达和 H2O2 生成增加。最后，我们评估了 H2O2 对 PCCL3 甲状腺细胞系 NIS 功能和 mRNA 水平的影响，结果显示其降低。因此，本研究表明甲状腺肿的大小与 NIS 调节之间存在关系，其机制可能涉及 I-X、TGFβ、NOX4 和增加的 ROS 产生。
