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.
Wright
M C
MC
Department of Toxicology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, United Kingdom. m.c.wright@mds.qmw.ac.uk
Allenby
G
G
Paine
A J
AJ
D000818:Animals; D001665:Binding Sites; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism*; D003907:Dexamethasone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004224:Diterpenes; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000084562:Retinyl Esters; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000378:metabolism*; D014801:Vitamin A / Q000031:analogs & derivatives / Q000494:pharmacology; D014802:Vitamin A Deficiency / Q000201:enzymology / Q000378:metabolism*
D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; C004180:dexamethasone 21-phosphate; C009166:retinol acetate; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C022657:steroid hormone 6-beta-hydroxylase