Glucocorticoid and mineralocorticoid receptors and corticosteroid homeostasis are potential targets for endocrine-disrupting chemicals

Abstract

Endocrine-disrupting chemicals (EDCs) have received significant concern, since they ubiquitously exist in the environment and are able to induce adverse health effects on human and wildlife. Increasing evidence shows that the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR), members of the steroid receptor subfamily, are potential targets for EDCs. GR and MR mediate the actions of glucocorticoids and mineralocorticoids, respectively, which are two main classes of corticosteroids involved in many physiological processes. The effects of EDCs on the homeostasis of these two classes of corticosteroids have also gained more attention recently. This review summarized the effects of environmental GR/MR ligands on receptor activity, and disruption of corticosteroid homeostasis. More than 130 chemicals classified into 7 main categories were reviewed, including metals, metalloids, pesticides, bisphenol analogues, flame retardants, other industrial chemicals and pharmaceuticals. The mechanisms by which EDCs interfere with GR/MR activity are primarily involved in ligand-receptor binding, nuclear translocation of the receptor complex, DNA-receptor binding, and changes in the expression of endogenous GR/MR genes. Besides directly interfering with receptors, enzyme-catalyzed synthesis and prereceptor regulation pathways of corticosteroids are also important targets for EDCs. The collected evidence suggests that corticosteroids and their receptors should be considered as potential targets for safety assessment of EDCs. The recognition of relevant xenobiotics and their underlying mechanisms of action is still a challenge in this emerging field of research.