Effect of triclosan, triclocarban, 2, 2′, 4, 4′-tetrabromodiphenyl ether, and bisphenol A on the iodide uptake, thyroid peroxidase activity, and expression of genes involved in thyroid hormone synthesis. (April 2016)

• Record Type: Journal Article
• Authors: Wu, Yuanfeng; Beland, Frederick A.; Fang, Jia-Long
• Is Part Of: Toxicology in vitro. Volume 32(2016)
• Page Start: 310
• Page End: 319
• Publication Date: 2016-04
• Subjects: Thyroid disruptors -- Iodide uptake -- Thyroid hormone synthesis -- Thyroid peroxidase; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2016.01.014
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Triclosan, triclocarban, 2, 2′, 4, 4′-tetrabromodiphenyl ether (BDE-47), and bisphenol A (BPA) have been reported to disturb thyroid hormone (TH) homeostasis. We have examined the effects of these chemicals on sodium/iodide symporter (NIS)-mediated iodide uptake and the expression of genes involved in TH synthesis in rat thyroid follicular FRTL-5 cells, and on the activity of thyroid peroxidase (TPO) using rat thyroid microsomes. All four chemicals inhibited NIS-mediated iodide uptake in a concentration-dependent manner. A decrease in the iodide uptake was also observed in the absence of sodium iodide. Kinetic studies showed that all four chemicals were non-competitive inhibitors of NIS, with the order of K i values being triclosan < triclocarban < BDE-47 < BPA. The transcriptional expression of three genes involved in TH synthesis, Slc5a5, Tpo, and Tgo, and three thyroid transcription factor genes, Pax8, Foxe1, and Nkx2-1, was examined using quantitative real-time PCR. No significant changes in the expression of any genes were observed with triclosan or triclocarban. BDE-47 decreased the level of Tpo, while BPA altered the expression of all six genes. Triclosan and triclocarban inhibited the activity of TPO at 166 and > 300 μM, respectively. Neither BDE-47 nor BPA affected TPO activity. In conclusion, triclosan, triclocarban, BDE-47, and BPA inhibited iodide uptake, but had differential effects on the expression of TH synthesis-related genes and the activity of TPO. Highlights: Triclosan, triclocarban, BDE-47, and BPA inhibited iodide uptake in rat thyroid follicular cells. All four chemicals acted as non-competitive inhibitors of the sodium/iodide symporter. The chemicals exhibited differential effects on thyroid hormone synthesis gene expression. Thyroid peroxidase was not a primary target of the four chemicals.