Nuclear receptors are the major targets of endocrine disrupting chemicals

@article{Toporova2020NuclearRA,
  title={Nuclear receptors are the major targets of endocrine disrupting chemicals},
  author={Lucia Toporova and Patrick Balaguer},
  journal={Molecular and Cellular Endocrinology},
  year={2020},
  volume={502}
}
Endocrine disrupting chemicals (EDCs) are exogenous substances that are suspected to cause adverse effects in the endocrine system mainly by acting through their interaction with nuclear receptors such as the estrogen receptors α and β (ERα and ERβ), the androgen receptor (AR), the pregnan X receptor (PXR), the peroxisome proliferator activated receptors α and γ (PPARα, PPARγ) and the thyroid receptors α and β (TRα and TRβ). More recently, the retinoid X receptors (RXRα, RXRβ and RXRγ), the… 
Natural and synthetic retinoid X receptor ligands and their role in selected nuclear receptor action.
TLDR
This article summarizes both naturally occurring and synthetic ligands for nuclear retinoid X receptors and describes, predominantly in mammals, their role in molecular mechanisms within the cells, with a focus on triorganotin compounds.
Virtual screening of potentially endocrine-disrupting chemicals against nuclear receptors and its application to identify PPARγ-bound fatty acids
TLDR
A virtual screening method based on molecular docking for predicting potential endocrine-disrupting chemicals (EDCs) that bind to NRs is proposed and found that the consensus enrichment from multiple structures is better than or comparable to the best enrichment from a single structure.
Effect of selected bisphenol derivatives on nuclear receptor expression in ovarian cell line COV434
TLDR
The effect of bisphenols on COUP-TFII, Nurr1, and LRH-1 NRs was investigated for the first time and generally it was observed that BPs provoked any alterations in the expression of the selected NRs in COV434 cells, at specific concentrations and time points they might alter mRNA expression of certain NRs.
Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR
TLDR
The key features and mechanisms of CAR as a xenobiotic-sensing receptor, species differences and selectivity of CAR ligands, contribution of CAR to regulation hepatic metabolism, and evidence for CAR-dependent EDC action therein are reviewed.
In vitro assessment of pesticides capacity to act as agonists/antagonists of the thyroid hormone nuclear receptors
TLDR
RNA-seq analysis provided no evidence that some pesticides elicit a cellular response, which sometimes interferes with TH signaling, and their neurodevelopmental toxicity in mammals cannot be explained by an alteration of the response to TH.
A computational insight into endocrine disruption by polychlorinated biphenyls via non-covalent interactions with human nuclear receptors.
TLDR
This computational study suggests that PCBs may cause endocrine disruption via formation of non-covalent interactions with androgen, estrogen, glucocorticoid and thyroid hormone receptors.
Allosteric binding on nuclear receptors: Insights on screening of non-competitive endocrine-disrupting chemicals.
TLDR
This work systematically summarized the allosteric sites and underlying mechanisms based on existing studies, mainly regarding drugs belonging to the PPCP class, to drive high-throughput and accurate screening of potential EDCs with non-competitive effects.
Health effects associated with phthalate activity on nuclear receptors
TLDR
This review aims to summarize the known action of phthalates on different nuclear receptors and activate and interfere with the normal function of different peroxisome proliferator-activated receptors, receptors that have critical roles in lipid metabolism and energy homeostasis.
Perfluorinated Iodine Alkanes Induce Tissue-Specific Expression of Estrogen Receptor and Its Phosphorylation
Abstract Understanding the tissue-specific regulation of environmental endocrine disrupting chemicals (EDCs) on the expression and phosphorylation of estrogen receptors (ERs) is essential to fully
Theoretical study on endocrine disrupting effects of polychlorinated dibenzo‐p‐dioxins using molecular docking simulation
TLDR
Supporting evidence is provided that PCDD molecules may interfere with the endocrine system via binding interactions with some vital amino acid residues in the binding pockets of AR, ERs, GRs and TRs.
...
1
2
3
4
...

References

SHOWING 1-10 OF 107 REFERENCES
Structural and functional evidences for the interactions between nuclear hormone receptors and endocrine disruptors at low doses.
TLDR
Examples of 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 are presented to illustrate various means by which EDCs achieve high-affinity binding to NRs.
Insights into the activation mechanism of human estrogen-related receptor γ by environmental endocrine disruptors
TLDR
Biophysical characterizations coupled to molecular dynamics simulations suggested a mechanism through which ERRγ ligands would exhibit their agonistic properties by preserving the transcriptionally active form of the receptor while rigidifying some loop regions with associated functions.
Insights into the activation mechanism of human estrogen-related receptor gamma by environmental endocrine disruptors.
The estrogen-related receptor γ (ERRγ, NR3B3) is a constitutively active nuclear receptor which has been proposed to act as a mediator of the low-dose effects of a number of environmental
Functional profiling of bisphenols for nuclear receptors.
TLDR
It was showed that bisphenols differently modulated the activities of NRs, whereas many compounds of this family acted as AR, PR, GR and MR antagonists, which provide the guidelines for development of safer BPA substitutes with reduced hormonal activity.
A structural view of nuclear hormone receptor: endocrine disruptor interactions
TLDR
This work reviews recent studies showing the many ways in which EDCs interact with NHRs and impact their signaling pathways and suggests structure-based knowledge can be used to predict the endocrine-disrupting potential of environmental pollutants and may have applications in drug discovery.
Activation of RXR–PPAR heterodimers by organotin environmental endocrine disruptors
TLDR
It is shown that tributyltin (TBT) activates all three RXR–PPAR‐α, ‐γ, ‑δ heterodimers, primarily through its interaction with RXR.
Profiling of bisphenol A and eight its analogues on transcriptional activity via human nuclear receptors.
TLDR
Results suggested that BPA analogues demonstrate multiple effects via human nuclear receptors in a similar manner to BPA, and several analogues might have more potent endocrine-disrupting activity than does BPA.
A structural perspective on nuclear receptors as targets of environmental compounds
TLDR
A structural and mechanistic view of endocrine disrupting action using estrogen receptors α and β, (ERα/β), peroxisome proliferator activated receptor γ (PPARγ), and their respective environmental ligands as representative examples are provided.
Structural and Functional Profiling of Environmental Ligands for Estrogen Receptors
TLDR
The precise characterization of the interactions between major environmental pollutants and two of their primary biological targets provides rational guidelines for the design of safer chemicals, and will increase the accuracy and usefulness of structure-based computational methods, allowing for activity prediction of chemicals in risk assessment.
Mechanisms of endocrine disruption through nuclear receptors and related pathways
Abstract Endocrine-disrupting chemicals (EDCs) are a broad class of molecules present in our environment that are suspected to cause adverse effects in the endocrine system by interfering with the
...
1
2
3
4
5
...