Nuclear receptors are the major targets of endocrine disrupting chemicals

Mol Cell Endocrinol. 2020 Feb 15:502:110665. doi: 10.1016/j.mce.2019.110665. Epub 2019 Nov 21.

Abstract

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 constitutive androstane receptor (CAR) and the estrogen related receptor γ (ERRγ) have also been identified as targets of EDCs. Finally, nuclear receptors still poorly studied for their interaction with environmental ligands such as the progesterone receptor (PR), the mineralocorticoid receptor (MR), the glucocorticoid receptor (GR), the retinoic acid receptors (RAR α, RARβ and RARγ), the farnesoid X receptor (FXR) and the liver X receptors α and β (LXRα and LXβ) as well are suspected targets of EDCs. Humans are generally exposed to low doses of pollutants, therefore the aim of current research is to identify the targets of EDCs at environmental concentrations. In this review, we analyze recent works referring that nuclear receptors are targets of EDCs and we highlight which EDCs are able to act at low concentrations.

Keywords: Endocrine disruptors; Nuclear receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Endocrine Disruptors / adverse effects*
  • Environmental Pollutants / adverse effects*
  • Gene Expression Regulation / drug effects
  • Humans
  • Ligands
  • Receptors, Cytoplasmic and Nuclear / metabolism*

Substances

  • Endocrine Disruptors
  • Environmental Pollutants
  • Ligands
  • Receptors, Cytoplasmic and Nuclear