Effects of bisphenol A on thyroid hormone-dependent up-regulation of thyroid hormone receptor α and β and down-regulation of retinoid X receptor γ in Xenopus tail culture

We investigated effects of different concentrations (10− 7–10− 5 M) of bisphenol A (BPA), which is known as an estrogenic and anti-thyroid hormonal endocrine disrupter, on the expression of thyroid hormone receptor (TR) α and β and retinoid X receptor (RXR) γ mRNA in tails of stage 52–54 Xenopus tadpoles in organ culture in the presence or absence of different concentrations of triiodo-thyronine (T3). In the absence of T3, BPA at any concentration examined did not show remarkable effects on tail length but blocked 10− 7 M T3-induced tail resorption in a concentration-dependent manner. Semi-quantitative analyses of TRα and TRβ mRNAs by RT-PCR in the tail specimens indicated that BPA shows an apparent antagonistic effect towards the receptors and reduced their mRNA levels relative to controls. When administered together with 10− 7 M T3, the antagonistic effects of BPA were detected more clearly and dose-dependently. While BPA prevented the autoinduction of both TRα and TRβ genes by T3, the effect was less marked on TRα than on TRβ. BPA also moderately suppressed RXRγ gene expression. Gene expression of RXRγ, a partner for heterodimer formation of TRs, was supressed by T3 alone and also by BPA alone, but no additive effects were observed so far as studied. The present study indicates that a relatively low concentration of BPA, 10− 7 M, as compared with those examined previously (10− 5 to 10− 4 M) by us and other investigators, acts as an antagonist of T3 through suppression of TRα and TRβ gene expression in Xenopus tail in culture.