Barker E V, Hume R, Hallas A, Coughtrie W H
Department of Biochemical Medicine, University of Dundee, Ninewells Hospital and Medical School, Scotland, United Kingdom.
Endocrinology. 1994 Feb;134(2):982-9. doi: 10.1210/endo.134.2.8299591.
The sulfation of the adrenal steroid dehydroepiandrosterone (DHEA) is a critical step in the provision of substrates for estrogen biosynthesis by the placenta during pregnancy. This enzyme reaction is catalyzed by a cytosolic sulfotransferase (ST) found in many key body tissues, and we have examined the ontogeny and localization of expression of this important enzyme in three tissues: the liver, adrenal, and kidney. Hepatic DHEA ST expression increased with advancing gestational age before reaching near-adult levels in the early postnatal period, suggesting an increased requirement for this enzyme in the liver as development progresses, whereas in the adrenal and kidney there was no obvious ontogenic pattern. The enzyme was expressed at a 5-fold higher level in the adrenal than in the liver and some 40-fold higher than in the kidney. Comparison of enzyme activity measurements and quantitation of the expression of DHEA ST by immunodot blot analysis with an anti-DHEA ST antibody preparation demonstrated the fragility of the enzyme activity and suggested that immunoquantitation was a superior method for assessment of levels of expression of this enzyme in widely different tissue sources. Examination of the localization of DHEA ST in these tissues by immunohistochemistry showed that in liver, DHEA ST was expressed in embryonic hepatocytes and continued to be expressed in these cells into adulthood, when there was some concentration of immunostaining around central veins. In the fetus, the adrenal enzyme was expressed in the fetal zone, whereas in adult tissue, staining was localized principally to the zona reticularis. Renal DHEA ST was present in the proximal and distal tubules, loops of Henle, collecting ducts, and their progenitors, but was at no time expressed in the vascular glomerulus. In light of the broad substrate specificity of this enzyme toward other steroids, in particular bile acids and cholesterol, the information presented forms a strong basis for further studies into the role of DHEA ST in modulating the activity of a number of biologically active and potentially toxic steroids in the developing human.
肾上腺类固醇脱氢表雄酮（DHEA）的硫酸化是孕期胎盘为雌激素生物合成提供底物的关键步骤。这种酶反应由一种存在于许多关键身体组织中的胞质硫酸转移酶（ST）催化，我们已经研究了这种重要酶在肝脏、肾上腺和肾脏这三种组织中的个体发生及表达定位。肝脏中DHEA ST的表达随着胎龄增加而升高，在出生后早期达到接近成人的水平，这表明随着发育进程肝脏对该酶的需求增加，而在肾上腺和肾脏中则没有明显的个体发生模式。该酶在肾上腺中的表达水平比肝脏高5倍，比肾脏高约40倍。通过用抗DHEA ST抗体制备物进行免疫斑点印迹分析来比较酶活性测定和DHEA ST表达的定量，结果表明该酶活性不稳定，提示免疫定量是评估这种酶在广泛不同组织来源中表达水平的更好方法。通过免疫组织化学检查这些组织中DHEA ST的定位发现，在肝脏中，DHEA ST在胚胎肝细胞中表达，并在成年期这些细胞中持续表达，此时中央静脉周围有一些免疫染色集中。在胎儿中，肾上腺酶在胎儿带中表达，而在成人组织中，染色主要定位于网状带。肾脏DHEA ST存在于近端和远端小管、髓袢、集合管及其祖细胞中，但在血管球中从未表达。鉴于该酶对其他类固醇，特别是胆汁酸和胆固醇具有广泛的底物特异性，所提供的信息为进一步研究DHEA ST在调节发育中的人类体内多种生物活性和潜在有毒类固醇活性中的作用奠定了坚实基础。
