Bisphenol analogues induce thyroid dysfunction via the disruption of the thyroid hormone synthesis pathway

Bisphenol analogues are widely used in industrial and daily-use consumer products having imperfect thyroid hormones (THs) structures. Widespread exposure interferes with thyroid-related health outcomes in human. The mechanisms of disruption on TH synthesis and subsequent thyroid dysfunction by different bisphenol analogues remain unclear. Here, we evaluated bisphenol-induced thyroid endocrine disruption in C57BL/6 mice at doses of 0.002, 0.02, 2, and 20 mg/kg body weight/day (BW/d) for five consecutive weeks. Administration of 20 mg/kg BW/d bisphenol S (BPS) and 2 mg/kg BW/d tetrabromobisphenol S (TBBPS) significantly increased serum thyrotropin (TSH) levels to 1.21-fold and 1.20-fold of control group, respectively, indicating that bisphenols induced thyroid dysfunction in mice. Height of the thyroid follicle epithelium significantly increased to 1.27-, 1.24-, 1.26-, and 1.36-fold compared to control group with BPA, BPS, TBBPA, and TBBPS at 20 mg/kg BW/d, respectively, indicating impairment of the thyroid gland structure, and TBBPS showed potent effect. Exposure to bisphenol analogues of 0.02 mg/kg BW/d downregulated the protein expression levels of thyrotropin receptor, the sodium/iodide symporter, thyroperoxidase. The TH-dependent effects were further determined using the T-Screen assay at 10−11 M to 10−5 M concentrations. Bisphenol analogues significantly decreased TH-dependent GH3 cell proliferation, indicating the antagonistic activity of bisphenol analogues. The gene responsible for THs synthesis of thyrotropin releasing hormone receptor and TSH were upregulated, but downregulation of thyroid receptor β was observed. Our results suggest that bisphenol analogues distinctly induce thyroid dysfunction via TH synthesis, implying adverse effect of bisphenol analogues on TH homeostasis and subsequent physiological processes. [Display omitted] •Exposure to bisphenol analogues for 5 wk. increased TSH levels and caused thyroid dysfunction in mice.•Bisphenol analogues promoted follicular epithelial height and impaired the thyroid structure.•Bisphenol analogues down-regulated key protein expression of THs synthesis in mice (TSHR, TG, TPO and NIS).•THs-dependent cell proliferation and gene expression were disturbed by bisphenol analogues in GH3 cells.