Polychlorinated biphenyl exposure and CYP19 gene regulation in testicular and adrenocortical cell lines

Abstract

Exposure to polychlorinated biphenyls (PCBs) disturbs many estrogen-mediated biochemical processes. PCBs may cause these abnormalities by altering expression of the aromatase gene CYP19. This study demonstrated that high concentrations of PCB126 increased basal CYP19 mRNA abundance in mouse testicular Leydig I-10 cells and human adrenocortical H295R cells. Stimulating the cells with chorionic gonadotropin or 8-Br-cAMP concealed the estrogenic effect of PCB126. PCB126 is a powerful ligand for nuclear receptor AhR. Antagonizing the AhR activity of H295R by an inhibitor abolished PCB126-elicited CYP19 induction. However, PCB126 elevated basal CYP19 expression and aromatase activity in a slow progressive manner contrary to the sharp induction of the classic AhR target gene CYP1A1. Exposure of H295R to PCBs with different AhR activation abilities also varied CYP19 and CYP1A1 expression in dissimilar patterns, although the CYP19 mRNA levels were in line with the AhR activation abilities of the congeners. In contrast to PCB126, PCB39, which could not activate AhR and lacked effect on CYP1A1, significantly reduced CYP19 mRNA expression. AhR apparently played an important role in CYP19 gene regulation, but it might regulate CYP19 differently from CYP1A1 in the adrenocortical cells. Regardless of the action mechanism, PCB exposure increases risk for CYP19 dysregulation.