TY - JOUR T1 - Insights into Gender Bias: Rat Cytochrome P450 3A9 JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 703 LP - 709 DO - 10.1124/jpet.102.048090 VL - 305 IS - 2 AU - Sayeepriyadarshini Anakk AU - Chun Ying Ku AU - Mary Vore AU - Henry W. Strobel Y1 - 2003/05/01 UR - http://jpet.aspetjournals.org/content/305/2/703.abstract N2 - Some members of the CYP3A subfamily show gender-dependent expression. Using quantitative real-time polymerase chain reaction, we report that female rats have 28-fold higher CYP3A9 mRNA levels than males in liver and 3.8-fold higher in lung. Furthermore, the CYP3A9 expression profile in kidney exhibits a regio-specific distribution, i.e., a 10-fold higher expression in cortex compared with medulla. Also, we observed tissue-specific estrogen regulation of the CYP3A9 message. Estrogen treatment caused a significant up-regulation in liver and a marked down-regulation both in the cortex and medulla of the kidney. Upon ovariectomy, hepatic and brain CYP3A9 expression were reduced significantly, but a modest increase in kidney expression was observed. The effects of ovariectomy on CYP3A9 gene expression were reversed upon exogenous estrogen treatment. CYP3A protein levels and hepatic microsomal activity toward benzphetamine after various treatments showed changes parallel to CYP3A9 mRNA levels. We report for the first time that CYP3A9 levels change dramatically during the course of pregnancy. The American Society for Pharmacology and Experimental Therapeutics ER -