The effects of ammonium perchlorate on thyroid homeostasis and thyroid‐specific gene expression in rat

Abstract

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.

Dose-Response Relationship Between Orally Administered Ammonium Perchlorate and Urine Perchlorate Concentrations in Rats: Possible Biomarker to Quantify Environmental Ammonium Perchlorate Exposure on Thyroid Homeostasis

“…The effects of medium-and high-dose perchlorate on body weight gain in rat were presented in this study. These results were generally consistent with our previous findings 22 and other findings. 30,31 The current study has provided preliminary but important data for further study of perchlorate biomonitoring.…”

“…These results suggest that perchlorate could significantly decrease FT 4 levels and elevate TSH levels, which are consistent with previous studies. 1,22,23 Levels of T 3 , T 4 , and TSH in serum are considered to be biomarkers of perchlorate exposure on thyroid homeostasis for a long time. 19 Since perchlorate anions have an identical charge and similar ionic radius to iodide (I − ), perchlorate is known as a strong inhibitor of the sodium-iodide importer (NIS), which is the primary mechanism by which iodide enters thyroid follicle cells from the blood, and is the first step in the uptake of iodide into the thyroid leading to the formation of thyroid hormones.…”

Perchlorate Exposure and Thyroid Function in Ammonium Perchlorate Workers in Yicheng, China

“…The findings of the present study highlight the importance of iodine in thyroid homeostasis in occupationally AP exposed workers, as previously reported in animal experiments and in human studies [31,32]. Furthermore, the significant increase of median value of urinary perchlorate at the end of the shift was observed when compared with that of before the shift, which suggested the perchlorate in the urine can be used as the biomarker indicating exposure intensity.…”

Perchlorate exposure does not modulate temporal variation of whole-body thyroid and androgen hormone content in threespine stickleback

“…Perchlorate, a water soluble anion, is a known inhibitor of thyroid hormone (TH) synthesis (De Groef et al, 2006; Goleman et al, 2002; Leung et al, 2010; Wu et al, 2012). Perchlorate appears in a variety of sources relevant to human health, including contaminated drinking water, milk, and leafy vegetables (Dasgupta et al, 2006; Urbansky, 2002).…”