TY - JOUR T1 - 3-Methylcholanthrene Displays Dual Effects on Estrogen Receptor (ER) α and ERβ Signaling in a Cell-Type Specific Fashion JF - Molecular Pharmacology JO - Mol Pharmacol SP - 575 LP - 586 DO - 10.1124/mol.107.036384 VL - 73 IS - 2 AU - Elin Swedenborg AU - Joëlle Rüegg AU - Anne Hillenweck AU - Stefan Rehnmark AU - Malin Hedengran Faulds AU - Daniel Zalko AU - Ingemar Pongratz AU - Katarina Pettersson Y1 - 2008/02/01 UR - http://molpharm.aspetjournals.org/content/73/2/575.abstract N2 - The biological effects of 17β-estradiol (E2) are mediated by the two estrogen receptor (ER) isoforms ERα and ERβ. These receptors are ligand-inducible transcription factors that belong to the nuclear receptor superfamily. These receptors are also targets for a broad range of natural and synthetic compounds that induce ER activity, including dietary compounds, pharmaceuticals, and various types of environmental pollutants such as bisphenols and polychlorinated hydroxy-biphenyls. Here, we study the effect of the combustion byproduct 3-methylcholanthrene (3-MC) on ERα and ERβ. 3-MC is a compound identified previously as an activator of the aryl hydrocarbon receptor (AhR). Activation of AhR is traditionally associated with an inhibition of the E2 signaling network. In this study, we demonstrate that 3-MC is a cell-specific activator or inhibitor of E2 signaling pathways. We show that 3-MC acts as a repressor in some cells, presumably via the AhR, whereas it is a potent activator of ER activity in other cells. It is interesting that we demonstrate that the estrogenic effects of 3-MC are dependent on the ability of cells to metabolize parental 3-MC to alternative compounds. In summary, our results suggest that exposure to AhR ligands like 3-MC can lead to either activation or repression of E2 signaling, depending on the cellular context. The American Society for Pharmacology and Experimental Therapeutics ER -