Abstract
2,4,6-Tribromophenol (TBP) is a brominated flame retardant (BFR). Based on its affinity for transthyretin, TBP could compete with endogenous thyroid hormone. In this study, the effects of TBP on the thyroid hormone system were assessed in mice. Briefly, animals were exposed to 40 and 250 mg/kg TBP. Thyroid hormones were also administered with or without TBP. When mice were treated with TBP, deiodinase 1 (Dio1) and thyroid hormone receptor β isoform 2 (Thrβ2) decreased in the pituitary gland. The levels of deiodinase 2 (Dio2) and growth hormone (Gh) mRNA increased in response to 250 mg/kg of TBP, and the relative mRNA level of thyroid stimulating hormone β (Tshβ) increased in the pituitary gland. Dio1 and Thrβ1 expression in the liver were not altered, while Dio1 decreased in response to co-treatment with thyroid hormones. The thyroid gland activity decreased in response to TBP, as did the levels of free triiodothyronine and free thyroxine in serum. Taken together, these findings indicate that TBP can disrupt thyroid hormone homeostasis and the presence of TBP influenced thyroid actions as regulators of gene expression. These data suggest that TBP interferes with thyroid hormone systems
Highlights
The thyroid hormones, triiodothyronine (T3) and thyroxine (T4), are tyrosin-based hormones produced by the thyroid gland that are primarily responsible for the regulation of metabolism [1].The secretion of hormones is regulated by thyroid-stimulating hormone (TSH)
To investigate the effects of TBP in the mouse pituitary gland, we observed several genes related to thyroid hormones
Mice were exposed to TBP with or without thyroid hormones to investigate the competitive effects of TBP with blood transthyretin
Summary
The thyroid hormones, triiodothyronine (T3) and thyroxine (T4), are tyrosin-based hormones produced by the thyroid gland that are primarily responsible for the regulation of metabolism [1]. T3 binds to thyroid hormone receptor (THR) in target cells to regulate thyroid dependent genes [4]. BFRs have been reported to interfere with thyroid function by regulating various thyroid hormone mediated proteins, such as sodium iodide symporter, thyroperoxidase, thyroxine-binding globulin, transthyretin, deiodinase and THR. Tissue-specific expression of THR and Dio is regulated by serum thyroid hormone levels. Enzyme activity of Dio is highly induced by T3 in rodent liver, while THR is suppressed by thyroid hormones These negative or positive feedback systems are essential for regulating the blood or tissue thyroid hormone levels. Following exposure to TBP, several genes were up-regulated in females, while they were down-regulated in males because thyroid hormones have the opposite effect on estrogen response gene expression [17]. This study was conducted to investigate the effects of TBP on the thyroid system
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