The hypothalamus-pituitary-thyroid axis is disrupted by exposure to a mix of tributyltin and bisphenol S

Tributyltin is a biocide and bisphenol S is a plasticizer. The effects of the TBT + BPS mix on thyroid axis function are unknown. This study evaluated the effects of subacute exposure to TBT and BPS, both in mix and alone, in female young Wistar rats. Thyroid morphophysiology, gene expression, oxidative stress and collagen deposition were evaluated. TBT and BPS exposure resulted in a decrease in thyroid hormone levels, whereas TBT alone resulted in a decrease in TSH levels. The TBT + BPS group exhibited an increase in T₄ levels, a decrease in T₃ levels, a decrease in TPO activity, and an increase in TSHr mRNA expression. Deiodinase 1 (D1) and 2 (D2) were increased in the hypothalamus-pituitary-thyroid (HPT) axis (except for D2 in the pituitary gland) and in the liver of the TBT + BPS group, beside increases in the pituitary TRHr and thyroid ER mRNAs. The thyroid morphology of the TBT + BPS group revealed significant expansion of both the thyroid follicle and its surrounding tissue. In contrast, the TBT and BPS groups displayed numerous thyroid follicles undergoing fusion, a decrease in epithelial height and the epithelial/colloid ratio. The BPS group was the only group that exhibited increased collagen deposition. The TBT + BPS group demonstrated significant increases in the transcript levels of nrf2 and keap1. In all groups, the number of thiol groups decreased. There was an increase in SOD activity in the TBT + BPS group. Overall, subacute exposure to a mix deregulates the HPT axis, which correspondingly affects gene expression and causes enzymatic and morphological changes in the thyroid gland.