Feedback regulation of (Beta,Beta)-carotene 15,15'-monooxygenase by retinoic acid in rats and chickens

Beta-Carotene 15,15'-monooxygenase (formerly termed Beta-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 beta-carotene and its direct metabolites can regulate the enzyme activity in vivo. Bachmann et al found dose-dependent decreases in intestinal beta-carotene monooxygenase activity after oral administration to rats of retinyl acetate (up to -79%), beta-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 beta-carotene 15,15'-monooxygenase (Beta;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 beta-carotene was administered to rats pretreated with the two cytochrome P450 (CYP) inducers, pentobarbital and naphthoflavone, the intestinal beta CMOOX activity increased by 39%. In a transcriptional study in chickens, treatment with retinoic acid resulted in low expression of the intestinal beta CMOOX. Our data suggest that retinoids and carotenoids might regulate beta CMOOX expression by a transcriptional feedback mechanism via interaction with members of the RAR family.