Retinoid-dependent induction of the in vivo and in vitro metabolism of retinoic acid in tissues of the vitamin A-deficient hamster.

The metabolism of C3H]retinoic acid, both in uiuo and in vitro in a 10,000 X g supernatant preparation of small intestinal mucosa and liver of vitamin A-deficient hamsters, has been shown to be dependent upon pretreatment of the hamsters with retinoic acid. A proportional increase in both the in uiuo and the in vitro metabolism in the intestine and liv’er was found with inducing levels of retinoic acid i’n the range of 10 to 1000 pg/day for 3 days, orally, with the last dose given 24 h before death. In contrast, the in vitro activity of two epithelial target tissues of vitamin A, the testis and the trachea (in organ culture), was found to be independent of the induced state of the hamster. The kidney was totally inactive in the in vitro metabolism of retinoic acid regardless of the state of induction. The in vitro metabolism of retinoic acid in tissues from vitamin A-normal hamsters showed similar inductive effects with the exception of the liver which had a high basal level of activity in the uninduced state. The induction by retinoic acid approached the maximum level after 2 to 3 days of pretreatment and decayed back to base-line activity 2 days after the last inducing dose. An investigation into the effect of other retinoids (0.75 gmol/day for 3 days) on the in uiuo induction of the in vitro metabolism of retinoic acid in the intestinal mucosa of vitamin A-deficient hamsters revealed the following order of effectiveness as an inducer: 13-cisretinoic acid, retinoic acid ethyl ester, retinoyl glycine, all-trans-retinoic acid, retinal, retinyl acetate, 2-hydroxyethyl retinamide, and ethyl retinamide. The degree of induction of retinoic acid metabolism ranged from g-fold for 13-cis-retinoic acid to l.bfold for ethyl retinamide as compared to a vitamin A-deficient hamster.