DEVELOPMENTALLY-REGULATED EXPRESSION AND ACTIVITY OF 17-ALPHA-HYDROXYLASE C-17,20-LYASE CYTOCHROME-P450 IN RAT-LIVER/

We have investigated the developmental pattern of expression and activ ity of 17 alpha-hydroxylase/C-17,20-lyase cytochrome P450 (cytochrome P450c17) in the liver, stomach, duodenum, and testis of rats from day 18 of pregnancy to adulthood. In the male liver, the enzyme became det ectable at birth (135 pmol/mg protein.min) at a level comparable to th at in the testis (188 pmol/mg protein.min). The activity then increase d dramatically, reaching a peak at 8 days (691 pmol/mg protein.min), w hich was more than 4-fold the testicular levels in rats of the same ag e or in adults. Thereafter it declined steadily, becoming undetectable from puberty onward. The hepatic peak followed a depression in testic ular activity (58 pmol/mg protein.min) on day 6. Northern and immunobl ot analyses showed a good temporal correlation between enzyme activity and the occurrence of P450c17 messenger RNA (mRNA) and protein, The s ame patterns of mRNA and protein occurrence were observed in female ra t liver, indicating that the hepatic CYP17 expression is not sexually dimorphic. Sequencing confirmed a complete identity in the coding regi on between hepatic and gonadal mRNAs. Hepatic P450c17 mRNA, however, w as 150-200 bases longer than the gonadal counterparts. No significant expression of mRNAs encoding P450scc and P450arom was observed in live r of either sex at any age. In stomach and duodenum, enzyme activity w as much lower (maxima at 25 and 14 pmol/mg protein.min, respectively) than that in liver, but persisted from the time of weaning onward. It is suggested that the hepatic peak in P450c17 activity may serve to co nvert circulating progestogens into androgens for gonadal aromatizatio n during Sertoli and granulosa cell proliferation.