Insights into gender bias: rat cytochrome P450 3A9.
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.
Anakk
Sayeepriyadarshini
S
Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, P.O. Box 20708, Houston, TX 77225, USA.
Ku
Chun Ying
CY
Vore
Mary
M
Strobel
Henry W
HW
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015152:Blotting, Northern; D015153:Blotting, Western; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D017403:In Situ Hybridization; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D010052:Ovariectomy; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D014018:Tissue Distribution
D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol; D001189:Aryl Hydrocarbon Hydroxylases; C415842:Cyp3a9 protein, rat; D010089:Oxidoreductases, N-Demethylating