The adverse effects of chemicals exerted
via estrogen receptors (ER) and androgen receptors (AR) have been studied extensively in recent years. However, those occurring
via thyroid hormone receptors (TR) have not been studied enough. We examined the TR-binding activities of thyronine derivatives and alkylphenol derivatives (bisphenol A, parabens and antioxidants with
o-
t-butylphenol residue) using a yeast two-hybrid assay. In this assay system, the TR-binding activity of 3,5,3′-triiodo-L-thyronine (T
3) was detectable at concentrations as low as 3.0 × 10
-8 M and reached a plateau at 1.0 × 10
-6 M. The concentration of T
3 producing 10% of the activity stimulated at 1.0 × 10
-6 M (10% relative effective concentration, REC
10) was 2.1 × 10
-8 M. 3,5,3′,5′-tetraiodo-L-thyronine (T
4), 3,3′,5′-triiodo-L-thyronine (rT
3) and 3, 5-diiodo-L-thyronine (T
2) also exhibited TR-binding activities. The REC
10 values of these chemicals were 4.2 × 10
-8, 5.0 × 10
-7 and 1.0 × 10
-5 M, respectively.
o-Isopropylphenol and
o-
t-butylphenol exhibited TR-binding activities with REC
10 values of 3.1 × 10
-4 and 4.8 × 10
-5 M, respectively, whereas
t-butylbenzene, isopropylbenzene and the other chemicals tested had no detectable TR-bindng activity. These results suggest that a phenolic hydroxyl group and the
ortho-substituents may play important roles in the TR-binding activities of these chemicals. This assay system will be a useful tool for screening the TR-binding activities of chemicals.
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