Effect of vitamin A deficiency on the expression of low affinity glucocorticoid binding site activity and glucocorticoid-dependent induction of CYP3A2 in rat liver.

Maintenance of rats on a vitamin A-deficient diet resulting in undetectable levels of plasma retinol and significant reductions in relative testes weight compared to age-matched controls leads to the loss of liver membrane-bound low affinity glucocorticoid binding site (LAGS) activity without any effects on the levels of constitutively expressed CYP3A2 protein. Subsequent daily administration of retinol acetate to vitamin A-deficient rats results in the re-expression of LAGS activity to control levels by 7 days. To determine any role for the LAGS in the modulation of CYP3A2 expression by glucocorticoids, a single dose of dexamethasone 21-phosphate was administered to vitamin A-deficient rats and vitamin A-deficient rats induced to re-express LAGS by daily retinol acetate treatment. Retinol acetate administration alone induces CYP3A2 protein to apparent maximal levels since dexamethasone 21-phosphate does not further increase the induction response. However, CYP3A2 remains inducible to dexamethasone 21-phosphate in vitamin A-deficient rats. These data suggest that vitamin A status affects the expression of LAGS and CYP3A2 but that glucocorticoids regulate the induction of CYP3A2 by a mechanism(s) independent of their interaction with the LAGS.