Endocrine-disrupting Potential of Pesticides via Nuclear Receptors and Aryl Hydrocarbon Receptor

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概要

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• Nuclear receptors (NRs) and the aryl hydrocarbon receptor (AhR) form a ligand-dependent transcription factor that regulates the genes involved in key physiological functions such as cell growth and differentiation, development, homeostasis, and metabolism. These receptors are potential targets of endocrine-disrupting chemicals (EDCs). To date, many studies have shown that EDCs, such as plasticizers, pesticides, and dioxins, can function as ligands of NRs and AhR. In this review, we focus on recent studies showing that a variety of pesticides, intentionally released into the environment, have agonistic and/or antagonistic activity against NRs and AhR, and present our transactivation assay-based screening results for 200 pesticides against estrogen receptors (ERs), androgen receptor (AR), thyroid hormone receptors (TRs), pregnane X receptor (PXR), peroxisome proliferator-activated receptors (PPARs), and AhR. Our studies have shown that a number of pesticides possess ERα, ERβ, and PXR agonistic activity as well as AR antagonistic activity, whereas none of the pesticides affect the TRα1, TRβ1, and PPARγ-mediated signaling pathways. In addition, several of the 200 tested pesticides were found to have PPARα and AhR agonistic, and ERα and ERβ antagonistic activity. Although the activities of each of these compounds were weak compared to those of endogenous hormone or dioxins, the endocrine-disrupting potential of pesticides, particularly those which function against ERα/β, AR, and PXR, may reflect that of numerous environmental chemicals.

著者

• Kojima Hiroyuki

  Hokkaido Institute of Public Health

• Takeuchi Shinji

  Hokkaido Institute of Public Health

• Nagai Tadanori

  Hokkaido Institute of Public Health

関連論文

• Endocrine-disrupting Potential of Pesticides via Nuclear Receptors and Aryl Hydrocarbon Receptor
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