title: 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.
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 Ki 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.
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, USA.
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Beland
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, USA. Electronic address: jia-long.fang@fda.hhs.gov.
authors.forename: Jia-Long
authors.initials: JL
authors.lastname: Fang
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002224:Carbanilides / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D051858:Forkhead Transcription Factors / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D007454:Iodides / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D000072636:PAX8 Transcription Factor / Q000235:genetics; D010636:Phenols / Q000633:toxicity*; D017208:Rats, Wistar; D027981:Symporters / Q000235:genetics; D013954:Thyroglobulin / Q000235:genetics; D000072637:Thyroid Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics; D014260:Triclosan / Q000633:toxicity*; D000099209:Sodium-Iodide Symporters; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D002224:Carbanilides; D052244:Endocrine Disruptors; D051858:Forkhead Transcription Factors; D055768:Halogenated Diphenyl Ethers; D007453:Iodide Peroxidase; D007454:Iodides; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D010636:Phenols; D027981:Symporters; D013954:Thyroglobulin; D013963:Thyroid Hormones; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D014260:Triclosan; D000099209:Sodium-Iodide Symporters; C526350:FoxE1 protein, rat; C000614416:Nkx2-1 protein, rat; C499497:Pax8 protein, rat; C511295:2,2',4,4'-tetrabromodiphenyl ether; C009540:triclocarban; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Iodide uptake; Thyroid disruptors; Thyroid hormone synthesis; Thyroid peroxidase