Sex Differences in Constitutive Level of Renal Lauric Acid Hydroxylase Activities and CYP4A-Related Proteins in Mice

Abstract

The constitutive level of renal fatty acid hydroxylase was examined in ddY mice by measuring the activities of lauric acid ω- and (ω-1)-hydroxylase, (LA12H and La11H respectively). The activities of both LA12H and LA11H of male mice were significantly higher than those of female mice. This sex difference in renal lauric acid hydroxylase (LAH) activity exists in other strains of mice, including Balb/c, C57BL/6, C3H/HeN and C3H/HeJ. Renal LAH activities are at significantly low levels in both sexes of immature animals, but are sexually differentiated in the mature state. In male mice, orchiectomy caused a drastic decrease in renal LAH activities, and the activities were restored by testosterone treatment to above the level of the intact animal. In female mice, ovariectomy and estradiol treatment had no effect on the activities, but testosterone treatment caused an increase in the activities to the level of the intact male animal. These results suggested that testosterone is a key regulatory factor in the level of LAH activity in mouse kidney. The administration of dexamethasone and clofibrate affected the level of LAH activity. The above data are consistent with the level of CYP4A-related proteins (band H and L potein) measured by using anti-rat CYP4A1 antibodies. The antibodies inhibited both LA12H and LA11H activities. The level of band H protein was regulated by testosterone and dexamethasone. On the other hand, the level of band L protein was regulated by clofibrate. These results suggest that distinct modes of regulation exist in the level between band H and L protein in mouse kidney.