Insights into gender bias: Rat cytochrome P450 3A9

Sayeepriyadarshini Anakk, Chun Ying Ku, Mary Vore, Henry W. Strobel

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)703-709
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume305
Issue number2
DOIs
StatePublished - May 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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