M. Murray et al., RESTORATION OF CYTOCHROME-P450 2C11 IN VITAMIN-A-DEFICIENT RAT-LIVER BY EXOGENOUS ANDROGEN, The FASEB journal, 10(9), 1996, pp. 1058-1063
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.