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C R Biol. 2017 Sep - Oct;340(9-10):414-420. doi: 10.1016/j.crvi.2017.08.002.

Structural and functional evidences for the interactions between nuclear hormone receptors and endocrine disruptors at low doses.

Author information

1
Institut de recherche en cancérologie de Montpellier (IRCM), 34298 Montpellier, France; Inserm, U1194, 34298 Montpellier, France; Institut régional du cancer de Montpellier (ICM), 34298 Montpellier, France; Université de Montpellier, 34090 Montpellier, France. Electronic address: patrick.balaguer@montpellier.unicancer.fr.
2
Université de Montpellier, 34090 Montpellier, France; Inserm U1054, 34090 Montpellier, France; CNRS UMR5048, Centre de biochimie structurale, 34090 Montpellier, France.
3
Institut de recherche en cancérologie de Montpellier (IRCM), 34298 Montpellier, France; Inserm, U1194, 34298 Montpellier, France; Institut régional du cancer de Montpellier (ICM), 34298 Montpellier, France; Université de Montpellier, 34090 Montpellier, France.

Abstract

Endocrine-disrupting chemicals (EDCs) represent a broad class of exogenous substances that cause adverse effects in the endocrine system mainly by interacting with nuclear hormone receptors (NRs). Humans are generally exposed to low doses of pollutants, and current researches aim at deciphering the mechanisms accounting for the health impact of EDCs at environmental concentrations. Our correlative analysis of structural, interaction and cell-based data has revealed a variety of, sometimes unexpected, binding modes, reflecting a wide range of EDC affinities and specificities. Here, we present a few representative examples to illustrate various means by which EDCs achieve high-affinity binding to NRs. These examples include the binding of the mycoestrogen α-zearalanol to estrogen receptors, the covalent interaction of organotins with the retinoid X- and peroxisome proliferator-activated receptors, and the cooperative binding of two chemicals to the pregnane X receptor. We also discuss some hypotheses that could further explain low-concentration effects of EDCs with weaker affinity towards NRs.

KEYWORDS:

Endocrine disruptors; Low doses; Nuclear receptors

PMID:
29126514
DOI:
10.1016/j.crvi.2017.08.002
[Indexed for MEDLINE]
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