Yamada J, Sakuma M, Suga T
Department of Clinical Biochemistry, Tokyo College of Pharmacy, Japan.
Biochim Biophys Acta. 1992 Oct 27;1137(2):231-6. doi: 10.1016/0167-4889(92)90206-q.
Treatment of cultured rat-hepatocytes with 50 microM dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) for up to 5 days resulted in a progressive increase in peroxisomal beta-oxidation and carnitine acetyltransferase activity. After 5 days, the increases in activity were 2.6- and 4.8-fold for peroxisomal beta-oxidation and 11.7- and 17.1-fold for carnitine acetyltransferase over the initial activity, in DHEA- and DHEAS-treated cells, respectively. The stimulation of the activity of these enzymes by the respective agents was dose-related; it was maximum with 50 to 100 microM DHEA and 50 to 250 microM DHEAS, although DHEAS was more effective for stimulation than DHEA. Western blot analyses revealed the induction of acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme and carnitine acetyltransferase in the treated cells. Moreover, induction of fatty acid omega-hydroxylase proteins (P-450IVAS) was also revealed. These results indicate that DHEA and DHEAS act directly on hepatocytes. The induction of hepatic peroxisomal beta-oxidation enzymes and several other enzymes in rats administered with DHEA could be accounted for, at least in part, by the direct action of DHEA and its sulfate-conjugate (DHEAS) on liver cells.
用50微摩尔脱氢表雄酮（DHEA）及其硫酸盐（DHEAS）处理培养的大鼠肝细胞长达5天，导致过氧化物酶体β-氧化和肉碱乙酰转移酶活性逐渐增加。5天后，在DHEA和DHEAS处理的细胞中，过氧化物酶体β-氧化活性分别比初始活性增加2.6倍和4.8倍，肉碱乙酰转移酶活性分别比初始活性增加11.7倍和17.1倍。相应药物对这些酶活性的刺激呈剂量依赖性；在50至100微摩尔DHEA和50至250微摩尔DHEAS时达到最大值，尽管DHEAS比DHEA对刺激更有效。蛋白质印迹分析显示处理过的细胞中酰基辅酶A氧化酶、烯酰辅酶A水合酶/3-羟酰基辅酶A脱氢酶双功能酶和肉碱乙酰转移酶的诱导。此外，还发现了脂肪酸ω-羟化酶蛋白（P-450IVAS）的诱导。这些结果表明DHEA和DHEAS直接作用于肝细胞。给予DHEA的大鼠肝脏过氧化物酶体β-氧化酶和其他几种酶的诱导，至少部分可以由DHEA及其硫酸酯结合物（DHEAS）对肝细胞的直接作用来解释。
