Thyroid hormone disrupting potentials of bisphenol A and its analogues - in vitro comparison study employing rat pituitary (GH3) and thyroid follicular (FRTL-5) cells.

As adverse health effects of bisphenol A (BPA) become a growing public health concern, the chemicals substituting BPA have been increasingly used in everyday lives. BPA substitutes have been frequently detected in both environment and biota in increasing levels. However, very limited toxicological information is available for these chemicals. In the present study, thyroid disrupting effects of nine structural analogues of BPA were evaluated along with BPA, using rat pituitary (GH3) and thyroid follicular (FRTL-5) cells. Similar to BPA, its analogues caused significant down-regulation of tshβ, trα, trβ, dio1 or dio2 genes in GH3 cells, and some analogues, such as BPF, BPM or BPZ, showed even greater potency compared to BPA. In FRTL-5 cells, the genes responsible for hormone synthesis, e.g., pax8, nis, tg or tpo genes, exhibited over 1.5-fold up-regulation following exposure to BPA analogues, such as BPS. The effects on gene regulation was different by the cell line. Our results clearly show that the BPA substituting chemicals may influence thyroid hormone homeostasis by affecting thyroid regulation and hormone synthesis, often at lower doses compared to BPA. Thyroid effects of the BPA analogues deserve further investigations in experimental organisms and in human populations.