Nuclear Hormone Receptor Activity of Polybrominated Diphenyl Ethers and Their Hydroxylated and Methoxylated Metabolites in Transactivation Assays Using Chinese Hamster Ovary Cells

Kojima, Hiroyuki; Takeuchi, Shinji; Uramaru, Naoto; Sugihara, Kazumi; Yoshida, Toshihide; Kawa, Shigeyuki

doi:10.1289/ehp.0900753

Cited by 216 publications

(161 citation statements)

References 55 publications

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“…12,31,34 Using the reporter gene assay in Chinese hamster ovary cells, four OH-PBDEs (4 0 -OH-BDE-17, 4-OH-BDE-42, 4 0 -OH-BDE-49, 4-OH-BDE-90) did not show any agonistic activity, but 4-OH-BDE-90 exhibited a weak antagonistic activity for both TR isoforms. 35 In contrast, all the tested 18 OH-PBDEs showed 33 It is obvious that the results summarized above are fairly inconsistent, and both agonistic and antagonistic activities have been reported even for the same PBDE or OH-PBDE. This is probably because different cell lines were used in these studies.…”

Section: Thyroid Hormone Receptor Pathwaymentioning

confidence: 97%

Molecular toxicology of polybrominated diphenyl ethers: nuclear hormone receptor mediated pathways

Ren

Guo

2013

Environ. Sci.: Processes Impacts

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Polybrominated diphenyl ethers (PBDEs) are used in large quantities as flame retardant additives in commercial products. Bio-monitoring data show that PBDE concentrations have increased rapidly in the bodies of wildlife and human over the last few decades. Based on the studies on experimental animals, the toxicological endpoints of exposure to PBDEs are likely to be thyroid homeostasis disruption, neurodevelopmental deficits, reproductive ineffectiveness and even cancer. Unfortunately, the available molecular toxicological evidence for these endpoints is still very limited. This review focuses on the recent studies on the molecular mechanisms of PBDE toxicities carried out through the hormone receptor pathways, including thyroid hormone receptor, estrogen receptor, androgen receptor, progesterone receptor and aryl hydrocarbon receptor pathways. The general approach in the mechanistic investigation is to examine the in vitro direct binding of a PBDE with a receptor, the in vitro recruitment of a co-activator or co-repressor by the ligand-bound receptor, and the participation of the ligand in the receptor-mediated transcription pathways in cells. It is hoped that further studies in this area would provide more insights into the potential risks of PBDEs to human health. Environmental impactPBDEs are a class of chemicals used as ame retardant additives in a wide variety of industrial and commercial products. Rising levels of PBDEs have been detected in the human body. The toxicological endpoints of exposure to PBDEs are likely to be thyroid homeostasis disruption, neuro-developmental decits, reproductive ineffectiveness and even cancer. However, the available molecular toxicological evidence for these endpoints is still very limited. This review focuses on the recent studies on the molecular mechanisms of PBDE toxicities carried out through the hormone receptor pathways, including thyroid hormone receptor, estrogen receptor, androgen receptor, progesterone receptor and aryl hydrocarbon receptor pathways.

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Section: Thyroid Hormone Receptor Pathwaymentioning

confidence: 97%

Molecular toxicology of polybrominated diphenyl ethers: nuclear hormone receptor mediated pathways

Ren

Guo

2013

Environ. Sci.: Processes Impacts

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“…Kojima et al [58] both positions adjacent to the hydroxyl group. This structural factor seems to be a good predictor of a competitive inhibition mechanism, which could explain, at least partially, the antagonistic activity of OH-PBDEs at the TR.…”

Section: Trs?mentioning

confidence: 99%

Endocrine disruptors and thyroid hormone physiology

Jugan

Lévi

Blondeau

2010

Biochemical Pharmacology

215

115

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Endocrine disruptors are man-made chemicals that can disrupt the synthesis, circulating levels, and peripheral action of hormones. The disruption of sex hormones was subject of intensive research, but thyroid hormone synthesis and signaling are now also recognized as important targets of endocrine disruptors. The neurological development of mammals is largely dependent on normal thyroid hormone homeostasis, and it is likely to be particularly sensitive to disruption of the thyroid axis. Here, we survey the main thyroid-disrupting chemicals, such as polychlorinated biphenyls, perchlorates, and brominated flame retardants, that are characteristic disruptors of thyroid hormone homeostasis, and look at their suspected relationships to impaired development of the human central nervous system. The review then focuses on disrupting mechanisms known to be directly or indirectly related to the transcriptional activity of the thyroid hormone receptors.

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“…167,187,188 Cell based assays have shown that some OH-BDEs, including 3-OH-BDE-47, can inhibit T3 binding to TRs by antagonizing the receptor, whereas several other parent PBDEs and OH-BDEs have shown no TR affinity. 189,190 Another study showed TR antagonistic activity for BDE-209, -153, -154, -100, and PentaBDE. 191 Limited evidence has shown some OH-BDEs to behave as weak TR agonists.…”

Section: Binding To Thyroid Receptorsmentioning

confidence: 99%