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.