Dynamics of androstenedione metabolite formation in rat liver microsomes during temporal phenobarbital induction.

1. Formation of androstenedione (AD) 7 alpha-, 16 alpha-, 16 beta- and 6 beta-hydroxymetabolites produced in rat liver microsomes and differing by the duration of phenobarbital (PB) induction (temporal induction) has been studied. 2. Formation of 7 alpha-, 16 alpha- and 6 beta-metabolite is sexually differentiated during PB-induction. 3. The most dramatical changes were observed in the 16 beta-hydroxylase activity specific for cytochrome P-450b which increased in all rat groups investigated. 4. The immunochemical method using antibodies against P-450b/e was applied to measure its content in microsomes. 5. It was shown that the microsomal level of P-450b/e correlated (r = 0.63) with a 16 beta-hydroxylase activity in a narrow range of enzyme concentrations (from 0.16 to 0.32 nmol/mg). 6. In microsomal preparations with a higher level of P-450b/e the correlation is lower (r = 0.4). 7. The dependence of the P-450b catalytic activity on the P-450b to NADPH-cytochrome P-450 reductase relation is discussed.