Bisphenol A interferes with TTF-1 and PAX8 modulation of dual oxidase 2 human thyroid promoter activity

Bisphenol A (BPA) is an endocrine disruptor related to the increasing prevalence of goiter and thyroid malignancy. PAX8 and TTF-1 control the expression of the main thyroid differentiation markers, including dual oxidase (Duox) 2, that are essential for thyroid hormone biosynthesis. An in silico study proposed the molecular interaction of BPA with PAX8 and TTF-1, suggesting that BPA could interfere in the signaling of both transcription factors (TFs) in the thyroid. Moreover, functional studies showing the effect of BPA on the modulation of thyroid Duox 2 expression controlled by PAX8 and TTF-1 are missing. Herein, we aimed to verify the effect of 10−9 M BPA on the modulation of thyroid Duox 2 (ptx 41) promoter activity in transfected HEK 293 cells (2 × 105 cells/well), co-transfected with Pax8 and/or TTF-1. As expected, in the absence (vehicle) of BPA, Duox 2 activity was increased when cells were co-transfected with Pax8 and TTF-1. On the other hand, the stimulatory effect of Pax8 and TTF-1 on human Duox 2 short promoter activity was abolished in the presence of BPA. In conclusion, our results confirmed that BPA blunted the stimulatory effect of PAX8 and TTF-1, on Duox 2 short promoter activity, which could impair thyroid hormone biosynthesis. Once PAX8 and TTF-1 are vital for thyroid organogenesis and are involved in Duox 2 expression, our results highlight the importance of controlling the thyroid’s exposure to BPA.