Effects of bisphenol analogs on thyroid endocrine system and possible interaction with 17β-estradiol using GH3 cells

This study was conducted using a rat pituitary (GH3) cell line to understand the effects of bisphenol analogs (BPs) on the thyroid endocrine system, in the presence of 17β-estradiol (E2). In the first series of experiments, changes in cell proliferation were examined after exposure to each of ten BPs, in the absence or presence of a median effective concentration (6.4 × 10^-10 M) of triiodothyronine (T3). All tested BPs significantly increased cell proliferation, suggesting thyroid hormone (TH) agonistic effects of BPs. BPs did not potentiate the T3-induced cell proliferation at 48 h exposure, while several tested BPs including BPA, BPAF, BPB, BPF, BPS, and BPZ elicited a potentiating effect on the T3-induced cell proliferation at 96 h exposure. These results indicate that TH-antagonistic effects of BPs depend on the tested dose and exposure time. In the second set of experiments, one of the most potent BPs, i.e., BPAF, was selected, and its possible interaction with E2 on the thyroid endocrine system was evaluated. Co-exposure of GH3 cells to 10^-12 M E2 showed an additive-like effect. The extent of increase in cell proliferation was more pronounced with a combination of BPAF and E2 than with that of BPA and E2. Significant down-regulation of Trα, Trβ, and Dio2 genes and up-regulation of the Tshβ gene were observed in GH3 cells following co-exposure to BPAF and E2. Our results showed that some BP analogs might influence the thyroid endocrine system, and such perturbation appeared to be enhanced in the presence of E2.