Molecular mechanism(s) of endocrine-disrupting chemicals and their potent oestrogenicity in diverse cells and tissues that express oestrogen receptors

Abstract

Endocrine-disrupting chemicals (EDCs) are natural or synthetic compounds present in the environment which can interfere with hormone synthesis and normal physiological functions of male and female reproductive organs. Most EDCs tend to bind to steroid hormone receptors including the oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR). As EDCs disrupt the actions of endogenous hormones, they may induce abnormal reproduction, stimulation of cancer growth, dysfunction of neuronal and immune system. Although EDCs represent a significant public health concern, there are no standard methods to determine effect of EDCs on human beings. The mechanisms underlying adverse actions of EDC exposure are not clearly understood. In this review, we highlighted the toxicology of EDCs and its effect on human health, including reproductive development in males and females as shown in in vitro and in vivo models. In addition, this review brings attention to the toxicity of EDCs via interaction of genomic and non-genomic signalling pathways through hormone receptors.

Fig. 1

Potential mechanism(s) of endocrine-disrupting chemicals (EDC) action. In the ‘genomic pathway’ of EDC action, EDCs interfere with oestrogen (E2) binding to oestrogen receptors (ERs). EDCs bind to ERs instead of E2, and can thus affect the transcription of target genes in the nucleus by binding to the oestrogen response element (ERE) of target genes. The ‘non-genomic pathway’ of EDC action may occur through ER such as G protein-coupled receptor (GPR30) located in the cytoplasmic membrane. Activation of GPR30 by EDCs leads to rapid downstream cellular signalling. This induces subsequent stimulation of protein kinase activation and phosphorylation, which in turn may affect the transcription of target genes. The resulting changes by interaction between ERs and GPR30 in gene expression and intracellular signalling can cause cellular response without regulation, which may produce adverse effects of EDCs on organs.