Institute of Industrial Toxicology, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Environ Toxicol. 2012 Aug;27(8):445-52. doi: 10.1002/tox.20655. Epub 2010 Sep 29.
Perchlorate, a kind of inorganic chemical, is mainly used in defense industry and widely used in other civilian areas. It was well known that perchlorate exerts its thyrotoxicant effect on thyroid homeostasis via competitive inhibition of iodide uptake. However, some details of mechanism by which perchlorate disturb thyroid homeostasis are unknown and remain to be elucidated. The present study aimed to investigate if iodide insufficiency in the thyroid is the main mechanism by which perchlorate exerts its effect on the thyroid gland. We highlighted and measured the gene expression of NIS, Tg, and TPO which involved in thyroid hormone biosynthesis. Thyroid effects of perchlorate were identified by assessing different responses of these genes at the treatments of perchlorate and iodine deficiency. The results indicated that high dose perchlorate (520 mg kg(-1) b.wt.) can induce a significant decrease in body weight and cause hypertrophy of thyroid gland, with a decreased level of FT3, FT4 and a remarkable increased level of TSH. In addition, the significant decreased gene expression of Thyroglobulin (Tg) and thyroperoxidase (TPO) were both observed at the treatment of high dose perchlorate. These results suggested that perchlorate can suppress gene expression of Tg and TPO which directly involved in biosynthesis of thyroid hormones, and may therefore aggravate the perturbation of thyroid homeostasis in addition to competitive inhibition of iodide uptake.
高氯酸盐,一种无机化学物质,主要用于国防工业,也广泛应用于其他民用领域。高氯酸盐通过竞争性抑制碘摄取来发挥其甲状腺毒性作用,这一点早已众所周知。然而,高氯酸盐扰乱甲状腺内稳态的一些机制细节尚不清楚,仍需阐明。本研究旨在探讨甲状腺内碘不足是否是高氯酸盐对甲状腺发挥作用的主要机制。我们突出并测量了参与甲状腺激素生物合成的 NIS、Tg 和 TPO 的基因表达。通过评估高氯酸盐和碘缺乏处理对这些基因的不同反应,确定了高氯酸盐对甲状腺的影响。结果表明,高剂量高氯酸盐(520mgkg(-1)bw)可导致体重显著下降和甲状腺肿大,FT3、FT4 水平降低,TSH 水平显著升高。此外,在高剂量高氯酸盐处理时,还观察到甲状腺球蛋白(Tg)和甲状腺过氧化物酶(TPO)的基因表达显著下降。这些结果表明,高氯酸盐可抑制 Tg 和 TPO 的基因表达,这两种酶直接参与甲状腺激素的生物合成,因此除了竞争性抑制碘摄取外,还可能加重甲状腺内稳态的紊乱。