Species and sex differences of testosterone and nifedipine oxidation in liver microsomes of rat, dog and monkey

Publisher Website
Google Scholar
Abstract
1. Species and sex differences in testosterone hydroxylation and nifedipine oxidation in liver microsomes from rat, dog and monkey have been investigated. 2. The formation of 2α-, 2β-, 6β-, and 16α-hydroxytestosterone and androstenedione in the male rat was higher than that in the female rat. Microsomes prepared from the male rat oxidized nifedipine about eight times faster than did those from the female rat. In contrast, marked sex-related differences were not seen in the dog and monkey. 3. Nifedipine oxidase activity in rat, dog and monkey correlated significantly with the activities for both testosterone 2β-hydroxylation and 6β-hydroxylation, suggesting the involvement of P4503A isozymes in these reactions. The ratios of formation of the 2β- to 6β-hydroxytestosterone in male rat and monkey were 0·17 and 0·18 respectively, whereas that in dog was 0·46. The corresponding activity ratios catalysed by P450DPB-1, a P4503A isoform purified from dog liver microsomes, was 0·36. 4. The formation of 16β-hydroxytestosterone was higher than that of the 16α-hydro-lated metabolite in liver microsomes from monkey, whereas 16α-hydroxytestosterone was the predominant metabolite in the rat and dog, indicating species differences in stereoselectivity at the 16-position.