Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, Michigan.
J Clin Endocrinol Metab. 2018 Jan 1;103(1):320-327. doi: 10.1210/jc.2017-01525.
Dehydroepiandrosterone sulfate (DHEAS) is the most abundant steroid in human circulation, and adrenocorticotropic hormone (ACTH) is considered the major regulator of its synthesis. Pregnenolone sulfate (PregS) and 5-androstenediol-3-sulfate (AdiolS) have recently emerged as biomarkers of adrenal disorders.
To define the relative human adrenal production of Δ5-steroid sulfates under basal and cosyntropin-stimulated conditions.
Liquid chromatography-tandem mass spectrometry was used to quantify three unconjugated and four sulfated Δ5-steroids in (1) paired adrenal vein (AV) and mixed venous serum samples (21 patients) and (2) cultured human adrenal cells both before and after cosyntropin stimulation, (3) microdissected zona fasciculata (ZF) and zona reticularis (ZR) from five human adrenal glands, and (4) a reconstituted in vitro human 17α-hydroxylase/17,20-lyase/(P450 17A1) system.
Of the steroid sulfates, PregS had the greatest increase after cosyntropin stimulation in the AV (32-fold), whereas DHEAS responded modestly (1.8-fold). PregS attained concentrations comparable to those of DHEAS in the AV after cosyntropin stimulation (AV DHEAS/PregS, 24 and 1.3 before and after cosyntropin, respectively). In cultured adrenal cells, PregS demonstrated the sharpest response to cosyntropin, whereas DHEAS responded only modestly (21-fold vs 1.8-fold higher compared with unstimulated cells at 3 hours, respectively). Steroid analyses in isolated ZF and ZR showed similar amounts of PregS and 17α-hydroxypregnenolone in both zones, whereas DHEAS and AdiolS were higher in ZR (P < 0.05).
Our studies demonstrated that unlike DHEAS, PregS displayed a prominent acute response to cosyntropin. PregS could be used to interrogate the acute adrenal response to ACTH stimulation and as a biomarker in various adrenal disorders.
硫酸脱氢表雄酮（DHEAS）是人体循环中含量最丰富的甾体激素，促肾上腺皮质激素（ACTH）被认为是其合成的主要调节剂。孕烯醇酮硫酸酯（PregS）和 5-雄烯二醇-3-硫酸酯（AdiolS）最近已成为肾上腺疾病的生物标志物。
在基础和促皮质素刺激条件下，确定人类肾上腺 Δ5-甾体硫酸酯的相对产生情况。
采用液相色谱-串联质谱法，分别对（1）21 例患者配对的肾上腺静脉（AV）和混合静脉血清样本中的三种非共轭和四种硫酸化 Δ5-甾体进行定量，（2）促皮质素刺激前后培养的人肾上腺细胞，（3）从五个人肾上腺中微解剖的束状带（ZF）和网状带（ZR），（4）体外重建的人 17α-羟化酶/17,20-裂解酶/（P450 17A1）系统。
在促皮质素刺激后，AV 中 PregS 的增加幅度最大（增加 32 倍），而 DHEAS 的增加幅度适中（增加 1.8 倍）。在促皮质素刺激后，PregS 在 AV 中的浓度可与 DHEAS 相媲美（AV DHEAS/PregS，分别为促皮质素刺激前后的 24 和 1.3）。在培养的肾上腺细胞中，PregS 对促皮质素的反应最为剧烈，而 DHEAS 的反应仅适度（与未刺激细胞相比，分别在 3 小时时增加 21 倍和 1.8 倍）。在分离的 ZF 和 ZR 中的类固醇分析显示，两个区域中 PregS 和 17α-羟孕烯醇酮的含量相似，而 DHEAS 和 AdiolS 在 ZR 中的含量较高（P <0.05）。
我们的研究表明，与 DHEAS 不同，PregS 对促皮质素表现出明显的急性反应。PregS 可用于检测 ACTH 刺激下的肾上腺急性反应，并作为各种肾上腺疾病的生物标志物。
