Figure 4

Species-specific regulation of steroid hormone metabolism elicited by o , p '-DDT. (A) Overview of the role of CYP17A1 and CYP7B1 in steroid metabolism. CYP17A1 metabolizes pregnenolone and progesterone to produce DHEA and androstenedione, respectively. Hepatic CYP7B1 is involved in bile acid biosynthesis, and also responsible for 7α-hydroxylation of DHEA. (B) Hepatic Cyp17a1 and (C) Cyp7b1 mRNA levels in the o, p'-DDT-treated mouse and rat. QRT-PCR results relative to time-matched vehicle controls are shown as bars and presented as mean ± SE. Microarray results are represented as lines. o, p'-DDT induced Cyp17a1 and Cyp7b1 mRNAs in the mouse liver, while it did not affect in the rat liver [11]. The dashed line indicates the expression level of the time-matched vehicle control. The asterisk (*) indicates a significant (p < 0.05) difference from the time-matched vehicle controls for QRT-PCR, n = 5. (C) Representative Western analysis result for hepatic CYP17A1 protein in o, p'-DDT-treated mouse liver. CYP17A1 protein levels were induced at 18 and 24 h. Western analyses were performed on 3 independent biological replicates to verify the consistency of the results. C, control; T, 300 mg/kg o, p'-DDT. (D) Blood DHEA-S levels. DHEA-S level was significantly higher at 12 h following o, p'-DDT treatment compared to time-matched controls in the mouse, while it did not change in rats.