SPECIES AND SEX-DIFFERENCES OF TESTOSTERONE AND NIFEDIPINE OXIDATION IN LIVER-MICROSOMES OF RAT, DOG AND MONKEY

1. Species and sex differences in testosterone hydroxylation and nifed ipine oxidation in liver microsomes from rat, dog and monkey have been investigated. 2. The formation of 2 alpha-, 2 beta-, 6 beta-, and 16 alpha-hydroxytestosterone and androstenedione in the male rat was high er than that in the female rat. Microsomes prepared from the male rat oxidized nifedipine about eight times faster than did those from the f emale rat. In contrast, marked sex-related differences were not seen i n the dog and monkey. 3. Nifedipine oxidase activity in rat, dog and m onkey correlated significantly with the activities for both testostero ne 2 beta-hydroxylation and 6 beta-hydroxylation, suggesting the invol vement of P4503A isozymes in these reactions. The ratios of formation of the 2 beta- to 6 beta-hydroxytestosterone in male rat and monkey we re 0.17 and 0.18 respectively, whereas that in dog was 0.46. The corre sponding activity ratios catalysed by P450DPB-1, a P4503A isoform puri fied from dog liver microsomes, was 0.36. 4. The formation of 16 beta- hydroxytestosterone was higher than that of the 16 alpha-hydrolated me tabolite in liver microsomes from monkey, whereas 16 alpha-hydroxytest osterone was the predominant metabolite in the rat and dog, indicating species differences in stereoselectivity at the 16-position.