The affinity for thyroid hormone receptor (TR) of polybromodiphenyl ethers (PBDEs) and hydroxylated PBDEs was examined. 4-Hydroxy-2,2',3,4',5-pentabromodiphenyl ether (4-OH-BDE-90) and 3-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (3-OH-BDE-47) markedly inhibited the binding of triiodothyronine (1×10-10 M) to TR in the concentration range of 1×10-6-1×10-4 M. 2,3,4,5,6-Pentabromophenol (PBP) also showed an inhibitory effect at 1×10-5-1×10-4 M. However, 2,2',3,4,4',5'-hexabromodiphenyl ether (BDE-138), decabromodiphenyl ether (DBDE), 4-methoxy-2,2',3,4',5-pentabromodiphenyl ether (4-MeO-BDE-90), 4'-hydroxy-2,2',4,5'-tetrabromodiphenyl ether (4'-OHBDE-49), 4-hydroxy-2,2',3,4'-tetrabromodiphenyl ether (4-OH-BDE-42), 4'-hydroxy-2,2',4-tribromodiphenyl ether (4'-OH-BDE-17), 3'-hydroxy-2,4-dibromodiphenyl ether (3'-OH-BDE-7), 2,4,6-tribromophenol (TBP) and tetrabromohydroquinone (TBHQ) did not show affinity for TR. In contrast, 4'-OH-BDE-17 and 3'-OH-BDE-7 exhibited estrogenic activity in estrogen-responsive reporter assay using MCF-7 cells at the concentration of 1×10-5 M. However, adjacent bromo substitution of 3- or 4-hydroxylated PBDEs markedly decreased the estrogenic activity. These results suggest that hydroxylated PBDEs act as thyroid hormone-like agents, as well as estrogens, that a 4- or 3-hydroxyl group in PBDEs is essential for thyroid hormonal and estrogenic activities, and that adjacent dibromo substitution favors thyroid hormonal activity, but not estrogenic activity.
2008 by The Pharmaceutical Society of Japan