Suppression of the constitutive microsomal cytochrome P450 2C11 in male rat liver during dietary vitamin A deficiency

Abstract

The effect of dietary vitamin A deficiency on hepatic microsomal cytochrome P450 (P450) and associated oxidase activities was examined in the male rat. Intake of a deficient diet by weanling rats over 10 weeks led to a pronounced decline in hepatic and serum vitamin A concentrations to levels that were beneath the limits of detection. These changes occurred concurrently with a decrease in total microsomal P450 to 77% of vitamin A adequate control. Measurement of microsomal androstenedione metabolism revealed respective decreases in 16α- and 6β-hydroxylation pathways to 61 and 71% of adequate control; 7α-hydroxylation was not significantly decreased. Immunoquantitation of the principal catalyst of steroid 16α-hydroxylation, the androgen-dependent P450 2C11, indicated a significant decrease in the microsomal content of the enzyme to 78% of control (13.7 ± 0.9 ng/μg protein in deficient rat liver versus 17.5 ± 0.5 in adequate control; P < 0.005). Serum testosterone appeared lower in vitamin A deficient male rats, but did not attain statistical significance. Administration of a diet containing excess vitamin A (500IU/g) to rats for 10 weeks produced marked increases in hepatic vitamin A stores, but did not increase P450 2C11 activities. Thus, the expression and function of P450 2C11 is not related directly to hepatic vitamin A levels. The trend toward lower circulating androgen levels in male rats maintained on the deficient diet for 10 weeks may have a role in P450 2C11 down regulation, but other regulatory factors may also be disrupted in these animals.