Suppression of the constitutive microsomal cytochrome P450 2C11 in male rat liver during dietary vitamin A deficiency.
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 16 alpha- and 6 beta-hydroxylation pathways to 61 and 71% of adequate control; 7 alpha-hydroxylation was not significantly decreased. Immunoquantitation of the principal catalyst of steroid 16 alpha-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/micrograms 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 (500 IU/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.
Martini
R
R
Department of Medicine, University of Sydney Westmead Hospital, Australia.
Murray
M
M
D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D004032:Diet; D015536:Down-Regulation; D015870:Gene Expression; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000378:metabolism*; D014801:Vitamin A / Q000008:administration & dosage; D014802:Vitamin A Deficiency / Q000097:blood*
D014801:Vitamin A; D000735:Androstenedione; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase