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 (P450IIE 1) was obtained by screening a liver cDNA library with an oligonucleot ide representing a consensus sequence found in the orthologous rat, hu man, and rabbit sequences. The protein sequence deduced from the cDNA sequence had an identity of 93% to rat, 81% to rabbit, and 76% to huma n orthologous sequences. The highest levels of P450IIE1 mRNA were foun d in liver of both sexes, and male kidney. Developmentally, C57BL/6 fe male liver P450IIE 1 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 an d 4-fold by testosterone treatment, respectively, and the level in bot h tissues reached maximum levels between 12 h and 2 days after treatme nt. Nuclear run-on experiments demonstrated that testosterone treatmen t for 24-48 h resulted in a slight transcriptional activation of the P 450IIE1 gene in the kidney. However, the increase in transcription rat e was far below the increase in mRNA level, suggesting that much of th e induction occurs by posttranscriptional mechanisms. This process req uires the androgen receptor since mutant Tfm mice lacking receptor are not inducible.