Feedback Regulation of β,β-Carotene 15,15′-Monooxygenase by Retinoic Acid in Rats and Chickens

β,β-Carotene 15,15′-monooxygenase (formerly termed β,β-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 β-carotene and its direct metabolites can regulate the enzyme activity in vivo. We found dose-dependent decreases in intestinal β,β-carotene monooxygenase activity after oral administration to rats of retinyl acetate (up to −79%), β-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 β,β-carotene 15,15′-monooxygenase (βCMOOX) activity was not affected. Apo-12′carotenal and the retinoic acid receptor (RAR) α antagonist Ro 41-5253 significantly increased the intestinal enzyme activity by 55 and 94%, respectively. When β-carotene was administered to rats pretreated with the two cytochrome P450 (CYP) inducers, pentobarbital and naphthoflavone, the intestinal βCMOOX activity increased by 39%. In a transcriptional study in chickens, treatment with retinoic acid resulted in low expression of the intestinal βCMOOX. Our data suggest that retinoids and carotenoids might regulate βCMOOX expression by a transcriptional feedback mechanism via interaction with members of the RAR family.