SPECIES DIFFERENCES IN THE ALTERATION OF DRUG-METABOLIZING ACTIVITIES OF LIVER MICROSOMES BY THYROXINE TREATMENT

Abstract

The activities of drug-metabolizing enzymes of rat liver microsomes were altered by some unphysiological conditions (1-7). In previous papers we reported that the activities of hexobarbital hydroxylase and aminopyrine N-demethylase, which showed clear sex difference, were markedly decreased in the thyroxine treated male rats, whereas in female rats these activities were increased and the activity of aniline hydroxylase, which showed no clear sex difference, was increased in both male and female (3, 6). Similar results as observed in normal rats were obtained in male and female rats gonadectomized and treated with androgenic or anabolic hormones (3). These results, thus, indicate that the activities of hexobarbital hydroxylase and aminopyrine N-demethylase are dependent upon the anabolic action of male sex hormone and thyroxine probably decreases the androgen stimulated activity (3, 6). On the other hand, it has been supposed that the androgen-dependent regulation mechanism of microsomal drug-metabolizing activity is likely present only in rats, but it is lack in other species of animals (8-10). Thus, it is of interest to investigate whether or not the sex difference in the effect of thyroxine on the drug-metabolizing enzymes is only observed in rats and the effect of thyroxine in other species of male and female is similar to that observed in female rats. The possibility of this assumption was investigated with both male and female rats, mice and rabbits and reported in the present paper. Moreover, since the activity of drug-metabolizing enzymes was connected with the activity of NADPH-linked electron transport system of liver microsomes, the correlation of both activities under the thyroxine treatment was also investigated (4-7, 11-15).