Advances in Molecular Toxicology

The aryl hydrocarbon receptor (AHR) and estrogen receptors (ERs) are ligand-activated transcription factors and members of the basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) and nuclear receptor (NR) superfamilies, respectively. The bHLH-PAS and NRs regulate many vital physiological processes including metabolism, circadian rhythm, differentiation, development, and reproduction. However, both receptor families are also associated with numerous human diseases. Reciprocal crosstalk between AHR and ERs is proposed to both positively and negatively impact human health. ERs are the most important targets in the treatment of breast cancer. The AHR, which is activated by many environmental pollutants, natural/dietary compounds, and endogenous substances, is a negative regulator of ER function. The role of ERα in AHR signaling is less clear as it is known to exhibit cell-type and promoter-specific differences. In this chapter, we will highlight the current understanding of AHR and ER crosstalk and toxicity.