PMID: 8591733Nov 1, 1995Paper

Induction of "male-specific" cytochrome P450 isozymes in female rats by oxandrolone

Drug Metabolism and Disposition : the Biological Fate of Chemicals
M J WaskiewiczP E Thomas

Abstract

Oxandrolone (OXA) (5 alpha-androstan-2-oxa-17 alpha-methyl-17 beta-ol-3-one) is a clinically useful, synthetic, anabolic androgen steroid hormone. OXA was administered to rats orally twice daily for 3 days at 75 mg/kg to study the effect on hepatic cytochrome P450 (P450) isozymes. Western blots were performed on the hepatic microsomal fraction and probed with isozyme-specific monoclonal antibodies. Microsomes were also tested for catalytic activity in a testosterone metabolism assay. Data from Western blots revealed that, in female rats, there were increased levels of two male-specific isozymes, P4502C11 and P4503A2, as well as P4503A1. In contrast, male rats showed little or no change in expression of these P450 isozymes after OXA treatment. The 6 beta-hydroxylation of testosterone, which is catalyzed predominantly by P4503A1 and P4503A2, increased approximately 10-fold in female rats after treatment with OXA (from 0.05 +/- 0.01 to 0.52 +/- 0.05 nmol/min/mg protein), but only relatively small changes were seen in the male rats (from 1.02 +/- 0.05 to 1.38 +/- 0.07 nmol/min/mg protein). To investigate if the changes seen in P4503A1 and P4503A2 protein and activity were caused, at least in part, by an increase in mRNA levels, Nor...Continue Reading

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