Figure 1. Proposed mechanisms of crosstalk between AhR and ER signaling pathways.

AhR has been reported to inhibit ER activity through a combination of several different mechanisms: direct inhibition by the activated AhR/ARNT heterodimer through binding to inhibitory XRE (iXRE) present in ER target genes; squelching of shared coactivators, including ARNT; synthesis of an unknown inhibitory protein; increased proteasomal degradation of ER; and altered estrogen synthesis/metabolism through increase in aromatase, cytochromeP450 1A1 and 1B1 expression. Modified from Safe and Wormke, 2003.