Molecular mechanisms of dehydroepiandrosterone sulfate action on skeletal muscle cells

我们研究了脱氢表雄酮或脱氢表雄酮-S是否影响核受体的活性，特别是以CARβ为参照。给予脱氢表雄酮或脱氢表雄酮-S可增强肝细胞核提取物与视黄酸受体(Rare)、视黄酸受体β2(βRare)和过氧化物体增殖物激活受体(HD-PPRE)反应元件的结合。抗体超移位分析表明，结合的络合物与CAR-β-RXR杂二聚体结合。脱氢表雄酮或脱氢表雄酮-S处理后，肝脏中CAR-β靶基因Cyp2b10的表达增加，提示脱氢表雄酮或脱氢表雄酮-S在体内确实激活了CAR-β。提示脱氢表雄酮、脱氢表雄酮-S在体内可发生向CARβ配体的代谢转化，代谢产物可调节CARβ靶基因的表达。我们的结果为了解脱氢表雄酮/脱氢表雄酮-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.