Role of steroid sulfatase in steroid homeostasis and characterization of the sulfated steroid pathway: Evidence from steroid sulfatase deficiency
Role of steroid sulfatase in steroid homeostasis and characterization of the sulfated steroid pathway: Evidence from steroid sulfatase deficiency
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类固醇硫酸酯酶在类固醇稳态中的作用和硫酸化类固醇途径的特征：来自类固醇硫酸酯酶缺乏的证据
DOI：
10.1016/j.mce.2016.08.019
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发表时间：
2016
影响因子：
4.1
通讯作者：
Wudy SA
中科院分区：
文献类型：
--
作者：
Sánchez-Guijo A;Neunzig J;Gerber A;Hartmann MF;Schuppe HC;Traupe H;Bernhardt R;Wudy SA
类固醇硫酸酯酶(STS)活性对循环中硫化类固醇和非结合类固醇水平的影响仅部分为人所知。此外，硫化类固醇途径是与非结合类固醇途径平行的途径，使用相同的酶，以前从未详细描述过。类固醇硫酸酯酶缺乏症(STSD)患者不能在酶作用下将硫化类固醇转化为非结合形式，是阐明STS如何影响类固醇生物合成和研究硫化类固醇代谢的良好模型。我们对STSD血清中的未结合类固醇和硫化类固醇进行了量化，并将这些结果与健康对照组的血清数据进行了比较。大多数硫酸类固醇激素在STSD中增加。然而，雄烯二醇-3-硫酸酯和表雄酮硫酸盐在两组中显示出相似的水平，而雄酮硫酸酯浓度显著低于对照组。羟化形式的DHEAS和孕烯醇酮硫酸盐在STSD中被发现增加，这表明了一种促进硫化类固醇排泄的机制。STSD患者的睾酮水平正常，但胆固醇和脱氢表雄酮显著降低。此外，STSD患者的血清胆汁酸水平要高出三倍。各组类固醇浓度之间的相关性表明，男性体内的17α-羟基孕烯醇酮-3-硫酸酯主要是由DHEAS的前体孕烯醇酮硫酸酯和雄烯二醇-3-硫酸酯生物合成的。这些发现证实了两种类固醇合成途径的共存：一种是非结合类固醇途径，另一种是硫酸类固醇途径。每条途径都负责合成特定的类固醇。同等水平的睾酮，以及STSD中非结合前体水平的降低，支持睾酮主要是由硫化类固醇合成的。因此，STSD中睾酮的合成依赖于一种具有硫酸酯酶活性的酶，而不是STS。这项研究表明，STS是类固醇生物合成的关键参与者，调节循环胆固醇的可获得性。
The impact of steroid sulfatase (STS) activity in the circulating levels of both sulfated and unconjugated steroids is only partially known. In addition, the sulfated steroid pathway, a parallel pathway to the one for unconjugated steroids, which uses the same enzymes, has never been characterized in detail before. Patients with steroid sulfatase deficiency (STSD) are unable to enzymatically convert sulfated steroids into their unconjugated forms, and are a good model to elucidate how STS affects steroid biosynthesis and to study the metabolism of sulfated steroids. We quantified unconjugated and sulfated steroids in STSD serum, and compared these results with data obtained from serum of healthy controls. Most sulfated steroids were increased in STSD. However, androstenediol-3-sulfate and epiandrosterone sulfate showed similar levels in both groups, and the concentrations of androsterone sulfate were notably lower. Hydroxylated forms of DHEAS and of pregnenolone sulfate were found to be increased in STSD, suggesting a mechanism to improve the excretion of sulfated steroids. STSD testosterone concentrations were normal, but cholesterol and DHEA were significantly decreased. Additionally, serum bile acids were three-fold higher in STSD. Correlations between concentrations of steroids in each group indicate that 17α-hydroxy-pregnenolone-3-sulfate in men is mainly biosynthesized from the precursor pregnenolone sulfate and androstenediol-3-sulfate from DHEAS. These findings confirm the coexistence of two steroidogenic pathways: one for unconjugated steroids and another one for sulfated steroids. Each pathway is responsible for the synthesis of specific steroids. The equal levels of testosterone, and the reduced level of unconjugated precursors in STSD, support that testosterone is primarily synthesized from sulfated steroids. In consequence, testosterone synthesis in STSD relies on an enzyme with sulfatase activity other than STS. This study reveals that STS is a key player of steroid biosynthesis regulating the availability of circulating cholesterol.
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DOI：
10.1210/jc.2015-4101
发表时间：
2016-06
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Idkowiak J;Taylor AE;Subtil S;O'Neil DM;Vijzelaar R;Dias RP;Amin R;Barrett TG;Shackleton CH;Kirk JM;Moss C;Arlt W
通讯作者：
Arlt W
硫酸类固醇作为生物合成中间体的证据。
影响因子：
2.9
作者：
K. Roberts;L. Bandi;H. Calvin;W. Drucker;S. Lieberman
通讯作者：
S. Lieberman
DOI：
10.1210/jc.2014-3556
发表时间：
2015-04
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Oostdijk W;Idkowiak J;Mueller JW;House PJ;Taylor AE;O'Reilly MW;Hughes BA;de Vries MC;Kant SG;Santen GW;Verkerk AJ;Uitterlinden AG;Wit JM;Losekoot M;Arlt W
通讯作者：
Arlt W
影响因子：
4.4
作者：
Xie, Guoxiang;Wang, Yixing;Jia, Wei
通讯作者：
Jia, Wei
类固醇硫酸酯酶缺乏症患者血清中硫酸氧甾醇水平升高[S]
影响因子：
6.5
作者：
Sánchez-Guijo A;Hartmann MF;Schuppe HC;Traupe H;Wudy SA
通讯作者：
Wudy SA