Sex difference in the O-dealkylation activity of 7-hydroxycoumarin O-alkyl derivatives in liver microsomes of rats

Abstract

Sex differences in the O-dealkylation activities of O-alkyl derivatives of 7-hydroxycoumarin were compared using liver microsomes from male and female rats. The sex difference (male>female) in the O-depropylation activity was found to be greater than the sex differences in O-demethylation and O-deethylation activities. The magnitude of sex difference seen in the O-depropylation activity was diminished after pretreatment of rats with spironolactone, phenobarbital, isosafrole or 3-methylcholanthrene. The latter two inducers were much more effective than the former in enhancing the activity. The sex differences in the O-dealkylation activities were also seen when the activities were measured in the presence of cumene hydroperoxide instead of NADPH. The sex difference of the O-depropylation activity remained essentially unchanged by the fortification of male and female microsomes with purified NADPH-cytochrome c (P-450) reductase. The difference was also seen when reconstituted with cyto- chrome P-450 partially purified from both male and female rats by means of ω-amino- n-octyl Sepharose 4B and hydroxylapatite columns. The addition of 7,8-benzoflavone to the incubation mixture resulted in the increased magnitude of sex difference in the O-depropylation activity. From these results, we confirm that one or more cytochrome P-450 species other than a cytochrome P-450 species sensitive to 7,8-benzoflavone are present in male microsomes in higher amounts than in female microsomes.