PT - JOURNAL ARTICLE AU - Samar H. Gerges AU - Ayman O.S. El-Kadi TI - <strong>Sexual Dimorphism in the Expression of Cytochrome P450 Enzymes in Rat Heart, Liver, Kidney, Lung, Brain, and Small Intestine</strong> AID - 10.1124/dmd.122.000915 DP - 2022 Jan 01 TA - Drug Metabolism and Disposition PG - DMD-AR-2022-000915 4099 - http://dmd.aspetjournals.org/content/early/2022/09/18/dmd.122.000915.short 4100 - http://dmd.aspetjournals.org/content/early/2022/09/18/dmd.122.000915.full AB - Cytochrome P450 (CYP) enzymes are monooxygenases that are expressed hepatically and extrahepatically and play an essential role in xenobiotic metabolism. Substantial scientific evidence indicates sex-specific differences between males and females in disease patterns and drug responses, which could be attributed, even partly, to differences in the expression and/or activity levels of CYP enzymes in different organs. In this study, we compared the mRNA and protein expression of CYP enzymes in different organs of male and female Sprague Dawley rats by real-time polymerase chain reaction and Western blot techniques. We found significant sex and organ-specific differences in several enzymes. Hepatic Cyp2c11, Cyp2c13, and Cyp4a2 showed male-specific expression, while Cyp2c12 showed female-specific expression. Cyp2e1 and Cyp4f enzymes demonstrated higher expression in the female heart and kidneys compared to males; however, they showed no significant sexual dimorphism in the liver. Male rats showed higher hepatic and renal Cyp1b1 levels. All assessed enzymes were found in the liver, but some were not expressed in other organs. At the protein expression level, CYP1A2, CYP3A, and CYP4A1 demonstrated higher expression levels in the females in several organs including the liver. Elucidating sex-specific differences in CYP enzyme levels could help better understand differences in disease pathogeneses and drug responses between males and females, and thus improve treatment strategies. Significance Statement Significance statement: In this study, we characterized the differences in the mRNA and protein expression levels of different CYP enzymes between male and female rats in the heart, liver, lung, kidney, brain, and small intestine. We demonstrated unique sex-specific differences in the different organs. This study is considered a big step towards elucidating sex-specific differences in CYP enzyme levels, which is largely important for achieving a better understanding of differences between males and females in diseases processes and treatment outcomes.