Sex and strain differences in constitutive expression of fatty acid ω-hydroxylase (CYP4A-related proteins) in mice

The constitutive expression of hepatic fatty acid hydroxylase was examined in both sexes of ddY mice by measuring the activities of lauric acid ω-hydroxylase (LAH). The activity of male mice was significantly higher than that of female mice. Such a sex difference of hepatic LAH activity was not observed in other strains of mice, including BALB/c and C57BL/6. To examine whether decreased total P450 activities caused low LAH activity levels in female ddY mice, ethoxycoumarin O-deethylase activity, which is exhibited by many P450s, was measured in both sexes of mice. This activity had no sex difference. The developmental regulation of hepatic fatty acid hydroxylase was then examined by making consecutive measurements of LAH activity in ddY mice. The activity is the same in immature male and female mice, but is differentiated in the sexually mature state. Furthermore, in male mice, orchiectomy caused a dramatic decrease in hepatic LAH activity and the activity was restored by testosterone treatment to the level of the intact animal. In female mice, ovariectomy and estradiol treatment had no effect on the activity, but testosterone treatment caused an increase in the activity. The above data are consistent with the constitutive expression of CYP4A-related proteins measured by using anti-rat CYP4A1 polyclonal antibody. Anti-CYP4A1 antibody inhibited LAH activity, but not lauric acid (ω-1)-hydroxylase activity. These results suggest that some factors associated with male sex hormone are involved in the regulation of hepatic fatty acid ω-hydroxylase in ddY mice.