In vivo activation of the constitutive androstane receptor β (CARβ) by treatment with dehydroepiandrosterone (DHEA) or DHEA sulfate (DHEA‐S)

We investigated whether dehydroepiandrosterone (DHEA) or DHEA‐sulfate (S) affected the activities of nuclear receptors, with special reference to constitutive androstane receptor β (CARβ). Administration of DHEA or DHEA‐S enhanced the DNA binding of hepatic nuclear extracts to responsive elements for the retinoic acid receptor, the retinoic acid receptor β 2 and the peroxisome proliferator activated receptor. The bound complexes were shown to be the CARβ‐RXR heterodimer by antibody‐supershift assays. The expression of a target gene of CARβ, Cyp2b10, was increased in liver by DHEA or DHEA‐S treatment, suggesting that DHEA or DHEA‐S actually activated CARβ in vivo. It was suggested that the metabolic conversion of DHEA, DHEA‐S to CARβ ligands could occur in vivo and the metabolites could regulate the expression of CARβ target gene expression. Our results provide new insights into the in vivo relationship between DHEA/DHEA‐S and CARβ activation.