Nutrient-Gene Interactions Feedback Regulation of , -Carotene 15,15 -Monooxygenase by Retinoic Acid in Rats and Chickens

-Carotene 15,15 -monooxygenase (formerly termed , -carotene 15,15 -dioxygenase, EC 1.13.11.21) catalyzes the conversion of provitamin A carotenoids to retinal in vertebrate tissues. In the present study, we investigated whether preformed vitamin A or -carotene and its direct metabolites can regulate the enzyme activity in vivo. We found dose-dependent decreases in intestinal , -carotene monooxygenase activity after oral administration to rats of retinyl acetate (up to 79%), -carotene (up to 79%), apo-8 -carotenal (up to 56%), all-trans retinoic acid (up to 88%), and 9-cis retinoic acid (up to 67%). Liver , -carotene 15,15 monooxygenase ( CMOOX) activity was not affected. Apo-12 carotenal and the retinoic acid receptor (RAR) antagonist Ro 41–5253 significantly increased the intestinal enzyme activity by 55 and 94%, respectively. When -carotene was administered to rats pretreated with the two cytochrome P450 (CYP) inducers, pentobarbital and naphthoflavone, the intestinal CMOOX activity increased by 39%. In a transcriptional study in chickens, treatment with retinoic acid resulted in low expression of the intestinal CMOOX. Our data suggest that retinoids and carotenoids might regulate CMOOX expression by a transcriptional feedback mechanism via interaction with members of the RAR family. J. Nutr. 132: 3616–3622, 2002.