The AhR is a ligand dependent transcription factor which belongs to the bHLH-PAS family of transcription factors. Together with it partner factor ARNT the AhR mediates the biological of numerous ligands includings dietary factors, tryptophane derivatives and environmental pollutants like polyaromatic hydrocarbons and poly-chlorinated dioxins.
Exposure to these environmental pollutants leads to, among other effects, disruption of hormonal signaling pathways. Ample scientific evidence has demonstrated that exposure to dioxin inhibits for example estrogen receptor signaling pathways.
One of the mechanisms behind the disruptive effects of dioxin on E2 signaling is due to recruitment of ARNT to the AhR, an event that lowers the intracellular pool of ARNT available for the estrogen receptors ERα and ERβ.
We have continued to study the mechanisms by which dioxin and other AhR ligands modulate estrogen receptor signaling. Using a combination of bioinformatics and molecular biology methods we have shown that AhR ligands can either activate or repress ERα or ERβ signaling depending on cell-context. This cell and ligand specific effects are depending on P450 enzymes and their ability to generate metabolites that activate ERα and/or ERβ transcription. Interestingly, our observations show that exposure to different AhR ligand activate different gene expression profiles and thus different cellular outcomes.
25 - 29 Apr 2009
European Society of Endocrinology