RESTORATION OF CYTOCHROME-P450 2C11 IN VITAMIN-A-DEFICIENT RAT-LIVER BY EXOGENOUS ANDROGEN

Down-regulation of microsomal androgen-dependent CYP2C11 is produced i n male rat liver by dietary vitamin A deficiency, Decreased circulatin g androgen concentrations also occur in vitamin A-deficient male rats, Both effects are prevented by addition of all-trans-retinoic acid to the diet, The present study evaluated directly whether androgen defici ency may be responsible for the down-regulation of 2C11 in vitamin A-d eficient male rats, The major finding was that subcutaneous administra tion of the androgen methyltrienolone (MT) during the final week of th e study restored CYP2C11 protein and its associated steroid 16 alpha-h ydroxylation activities to control levels; CYP2C11 mRNA was also resto red, Despite the efficient restoration of CYP2C11 at a pretranslationa l level, no alteration in vitamin A status was apparent and animals re mained vitamin A deficient after MT treatment, The possibility was ass essed that vitamin A can maintain the microsomal content of CYP2C11 in normal Liver, However, in contrast to MT, administration of ATRA to g onadectomized male rats did not restore 2C11 in liver, These findings establish that the major effect of vitamin A deficiency on CYP2C11 in male rat liver is mediated indirectly by androgen deficiency.