The glucocorticoid receptor represses, whereas C/EBPβ can enhance or repress transcription.

Retinoic acid (RA) counters insulin's metabolic actions. Insulin reduces liver RA biosynthesis by exporting FoxO1 from nuclei. RA induces its catabolism, catalyzed by CYP26A1. A CYP26A1 contribution to RA homeostasis with changes in energy status had not been investigated. We found that glucagon, cortisol, and dexamethasone decrease RA-induced transcription, thereby reducing RA oxidation during fasting. Interaction between the glucocorticoid receptor and the RAR/RXR coactivation complex suppresses expression, increasing RA's elimination half-life. Interaction between CCAAT-enhancer-binding protein beta (C/EBPβ) and the major allele of SNP rs2068888 enhances expression; the minor allele restricts the C/EBPβ effect on . The major and minor alleles associate with impaired human health or reduction in blood triglycerides, respectively. Thus, regulating transcription contributes to adapting RA to coordinate energy availability with metabolism. These results enhance insight into CYP26A1 effects on RA during changes in energy status and glucocorticoid receptor modification of RAR-regulated gene expression.