Figure 5

Potential species-specific responses to o , p' -DDT. In the rat liver, o, p'-DDT elicits PXR/CAR-mediated response, with negligible ER-mediated effects despite the established estrogenicity of o, p'-DDT in other target tissues (e.g., uterus). The absence of ER-mediated gene expression may be due, in part, to the inhibitory effects of CAR on ER. In contrast, o, p'-DDT elicits not only PXR/CAR-mediated responses but also ER-mediated effects such as the induction of Cyp17a1 and Cyp7b1 in the mouse liver. Gene expression profiling suggests that o, p'-DDT preferentially activates PXR in the mouse liver. Therefore, the inhibitory effects of CAR on ER-mediated signaling would be reduced in the mouse liver, allowing the activation of ER-mediated gene expression by o, p'-DDT. In addition, only mouse DHEA-S levels were increased, which could affect both endocrine and liver physiology. The induction of Cyp17a1 and Cyp7b1 may be involved in either the metabolism or disposition of DHEA, or the conversion of DHEA into other metabolites including neurosteroids.