Forbes K J, Hagen M, Glatt H, Hume R, Coughtrie M W
Department of Biochemical Medicine, University of Dundee, Ninewells Hospital and Medical School, Scotland, UK.
Mol Cell Endocrinol. 1995 Jul;112(1):53-60. doi: 10.1016/0303-7207(95)03585-u.
Dehydroepiandrosterone sulphate (DHEAS) is a major adrenal secretory product, particularly in the fetus where it serves as a substrate for oestrogen biosynthesis by the placenta. The enzyme in the adrenal responsible for synthesising DHEAS, hydroxysteroid sulphotransferase (HST), is therefore essential for human development. We have isolated a full-length cDNA clone, encoding human fetal adrenal HST, and constructed a stable cell line expressing it by transfection into V79 Chinese hamster lung fibroblast cells. This cDNA was essentially identical to that isolated from adult human liver, where the role of HST is less well understood. This recombinant cell line allowed determination of the substrate specificity and kinetic properties of this enzyme towards various steroid hormones, and by comparison of these activities with human liver cytosol we have shown that HST is the major sulphotransferase responsible for the sulphation of DHEA, androsterone and pregnenolone in man and that, functionally, the hepatic and adrenal enzymes are very similar. The expressed HST was also active with testosterone, cortisol (although at low levels) and the xenobiotic 17 alpha-ethinyloestradiol, but not with oestrone or 1-naphthol. We have therefore created a valuable resource for the study of this important enzyme.
硫酸脱氢表雄酮（DHEAS）是肾上腺的主要分泌产物，在胎儿中尤为如此，它是胎盘雌激素生物合成的底物。因此，肾上腺中负责合成DHEAS的酶——羟基类固醇磺基转移酶（HST），对人类发育至关重要。我们分离出了一个编码人胎儿肾上腺HST的全长cDNA克隆，并通过转染到V79中国仓鼠肺成纤维细胞中构建了一个稳定表达它的细胞系。这个cDNA与从成人肝脏中分离出的cDNA基本相同，而HST在成人肝脏中的作用还不太清楚。这个重组细胞系能够确定该酶对各种甾体激素的底物特异性和动力学特性，通过将这些活性与人类肝脏胞质溶胶进行比较，我们发现HST是人体内负责硫酸化脱氢表雄酮、雄酮和孕烯醇酮的主要磺基转移酶，并且在功能上，肝脏和肾上腺中的酶非常相似。表达的HST对睾酮、皮质醇（尽管水平较低）和外源性17α-乙炔雌二醇也有活性，但对雌酮或1-萘酚没有活性。因此，我们为研究这种重要的酶创造了一个宝贵的资源。
