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. 2006:4:e016.
doi: 10.1621/nrs.04016. Epub 2006 Jul 7.

Estrogen receptor and aryl hydrocarbon receptor signaling pathways

Jason Matthews  1 , Jan-Ake Gustafsson
Affiliations

Estrogen receptor and aryl hydrocarbon receptor signaling pathways

Jason Matthews et al. Nucl Recept Signal. 2006.

Abstract

Estrogen receptors (ERs) and the aryl hydrocarbon receptor (AhR) are ligand activated transcription factors and members of the nuclear receptor and bHLH-PAS superfamilies, respectively. AhR is involved in xenobiotic metabolism and in mediating the toxic effects of dioxin-like compounds. Crosstalk has been observed among AhR and nuclear receptors, but has been most well studied with respect to ER signaling. Activated AhR inhibits ER activity through a number of different mechanisms, whereas ERalpha has been reported to have a positive role in AhR signaling. Here we will discuss recent data revealing that dioxin bound AhR recruits ERalpha to AhR regulated genes. We will also consider the implications of ER recruitment to AhR target genes on ER and AhR signaling.

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Figures

Figure 1
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.
Figure 2
Figure 2. Modulation of ER and AhR signaling via dioxin dependent interaction of ER with AhR
The association of ER with activated AhR can be viewed as two separate pathways. 1. Activated AhR recruits unliganded or liganded ERα away from ER regulated genes to AhR regulated genes, inhibiting estrogen signaling. The shuttling via the AhR may serve as a mechanism to regulate ER protein levels. 2. ERα has been shown to modulate AhR-dependent transcription, suggesting that ERα is an important regulator of AhR activity.
See this image and copyright information in PMC

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