Vitamin D is an essential nutrient that can be metabolized or absorbed from the diet, which has effects on various biological processes via the vitamin D receptor (VDR), a member of the nuclear hormone receptor superfamily of ligand-inducible transcription factors. To date, a number of VDR ligands that can activate this receptor have been developed, examples of which include vitamin D₃ derivatives that have been reported to have effects on inflammation and the cholesterol synthesis regulation in intestinal epithelium.
In the present study, we investigated the effects of a novel synthetic VDR agonist on pharmacokinetic gene expression using human iPS cell-derived intestinal organoids. Compared with vitamin D₃ treatment, the synthetic VDR agonist was found to increase the expression and activity of the drug-metabolizing enzyme CYP3A4, an indicator of intestinal functional maturation. Moreover, the the synthetic VDR agonist specifically increased the expression of the detoxification enzyme UGT1A and excretion transporter MRP2. These results suggest that our novel synthetic VDR agonist promotes the intestinal defense system.