SEX AND STRAIN DIFFERENCES IN MOUSE HEPATIC-MICROSOMAL COUMARIN 7-HYDROXYLASE ACTIVITY

Hepatic microsomal coumarin 7-hydroxylase activity has been determined in male and female mice of strains A/J, AKR, BALB/c, CBA/Ca, C3H/He, C57BL/6J, DBA/2 and 129. In males, coumarin 7-hydroxylase activity was highest in liver microsomes from DBA/Z mice and lowest in BALB/c mice. With female mice enzyme activity was highest in DBA/2 and 129 strains, intermediate in the CBA/Ca strain and comparatively low in the other five strains. Marked sex differences were observed in coumarin 7-hydroxylase activity with enzyme activity in female animals from strains DBA/2, 129 and CBA/Ca being 4.8-, 6.2- and 4.8-fold higher, respectively, than in male mice. In contrast, only minor sex and strain differences in levels of total microsomal cytochrome P-450 were observed. These results demonstrate marked sex and strain differences in mouse hepatic microsomal coumarin 7-hydroxylase activity. Such differences may be due to variations in particular cytochrome P-450 isoenzymes such as CYP2A5, not all of which can be explained by the known allelic difference in the Cyp2a-5 locus.