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Environmental endocrine disruptors and pregnane X receptor action: A review

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FOOD AND CHEMICAL TOXICOLOGY
卷 179, 期 -, 页码 -

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2023.113976

关键词

Environmental endocrine disruptors; Pregnane X receptor; Toxicological mechanism; Risk assessment

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This review summarizes the modulation of pregnane X receptor (PXR) by environmental endocrine disruptors (EEDs), including agonists and antagonists. The modular structure of PXR is described, and pharmacological variations of PXR among different species are discussed. Furthermore, the key role of PXR in endocrine regulation and the systematic summary of endocrine disruption by EEDs via PXR and its related pathways are provided.
The pregnane X receptor (PXR) is a kind of orphan nuclear receptor activated by a series of ligands. Environ-mental endocrine disruptors (EEDs) are a wide class of molecules present in the environment that are suspected to have adverse effects on the endocrine system by interfering with the synthesis, transport, degradation, or action of endogenous hormones. Since EEDs may modulate human/rodent PXR, this review aims to summarize EEDs as PXR modulators, including agonists and antagonists. The modular structure of PXR is also described, interestingly, the pharmacology of PXR have been confirmed to vary among different species. Furthermore, PXR play a key role in the regulation of endocrine function. Endocrine disruption of EEDs via PXR and its related pathways are systematically summarized. In brief, this review may provide a way to understand the roles of EEDs in interaction with the nuclear receptors (such as PXR) and the related pathways.

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