Molecular mechanisms of dehydroepiandrosterone sulfate action on skeletal muscle cells

我们研究了DHEA或DHEA-S是否影响核受体的活性，特别是CARβ。给予DHEA或DHEA-S可增强肝细胞核提取物与视黄酸受体（RARE）、视黄酸受体β2（β RARE）和过氧化物酶体增殖物激活受体（HD-PPRE）反应元件的DNA结合。通过抗体超位移测定显示结合的复合物与CARβ-RXR异源二聚体结合。通过DHEA或DHEA-S处理，CARβ的靶基因Cyp 2b 10在肝脏中的表达增加，表明DHEA或DHEA-S实际上在体内激活CARβ。提示DHEA、DHEA-S在体内可代谢转化为CARβ配体，其代谢产物可调节CARβ靶基因的表达。我们的研究结果为DHEA/ DHEA-S和CARβ激活之间的体内关系提供了新的见解。

We investigated whether DHEA or DHEA-S affected the activities of nuclear receptors, with special reference to CARβ. Administration of DHEA or DHEA-S enhanced the DNA binding of hepatic nuclear extracts to responsive elements for the retinoic acid receptor (RARE), the retinoic acid receptor β2 (β RARE) and the peroxisome proliferator activated receptor (HD-PPRE). The bound complexes were shown to 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.