Mouse ethanol-inducible cytochrome P-450 (P450IIE1). Characterization of cDNA clones and testosterone induction in kidney tissue.

A mouse cDNA clone for the ethanol-inducible cytochrome P-450 (P450IIE1) was obtained by screening a liver cDNA library with an oligonucleotide representing a consensus sequence found in the orthologous rat, human, and rabbit sequences. The protein sequence deduced from the cDNA sequence had an identity of 93% to rat, 81% to rabbit, and 76% to human orthologous sequences. The highest levels of P450IIE1 mRNA were found in liver of both sexes, and male kidney. Developmentally, C57BL/6 female liver P450IIE1 mRNA was detectable 1 day postpartum and reached steady-state levels in animals approximately 16-20 days of age. Kidney and adrenal gland P450IIE1 mRNA was found to be induced 25-50-fold and 4-fold by testosterone treatment, respectively, and the level in both tissues reached maximum levels between 12 h and 2 days after treatment. Nuclear run-on experiments demonstrated that testosterone treatment for 24-48 h resulted in a slight transcriptional activation of the P450IIE1 gene in the kidney. However, the increase in transcription rate was far below the increase in mRNA level, suggesting that much of the induction occurs by posttranscriptional mechanisms. This process requires the androgen receptor since mutant Tfm mice lacking receptor are not inducible.