Cell type-dependent agonist/antagonist activities of polybrominated diphenyl ethers.
There have been many concerns expressed regarding the possible adverse effects of thyroid hormone-disrupting chemicals including polychlorinated biphenyls and polybrominated diphenyl ethers (PBDEs), since thyroid hormones play crucial roles in normal vertebrate development. A vast amount of PBDEs have been used as flame retardants for the last two decades and our environment has been contaminated with them. Some PBDEs, especially hydroxylated PBDEs, reportedly show an affinity to the thyroid hormone receptor (TR) and act as thyroid hormone agonists, but in other studies they were reported to inhibit the actions of thyroid hormones. Therefore, in the present study, we investigated the binding affinities of PBDEs and their metabolites to TR and their ability to induce thyroid hormone-responsive transcription using luciferase reporter gene assays in two different cell lines, a pituitary cell line, MtT/E-2, and Chinese hamster ovary (CHO) cells. The binding assay showed that many of the examined PBDEs have significant affinity to TR. Interestingly, some of these PBDEs, such as 4'-OH-BDE-17 and 2'-OH-BDE-28, acted as agonists in the reporter gene assay in MtT/E-2 cells, while they acted as antagonists in CHO cells. Our results demonstrated that whether PBDEs and their metabolites are TR agonists or antagonists depends on the cell type used in the assay, which may suggest that the thyroid hormone-disrupting actions of PBDEs differ among target tissues or species.
Faculty of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
N
N
Nakamura
K
K
Matsubara
S
S
Sanoh
S
S
Ohta
N
N
Uramaru
S
S
Kitamura
M
M
Yamaguchi
K
K
Sugihara
N
N
Fujimoto
D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D052244:Endocrine Disruptors / Q000633:toxicity; D005411:Flame Retardants / Q000633:toxicity; D017930:Genes, Reporter; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D010902:Pituitary Gland / Q000166:cytology* / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D011988:Receptors, Thyroid Hormone / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013963:Thyroid Hormones / Q000819:agonists / Q000378:metabolism
D052244:Endocrine Disruptors; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones
Cell type-specific; Endocrine disruptors; MtT/E-2; PBDEs; Thyroid hormones