Expression profiling of human fetal cytosolic sulfotransferases involved in steroid and thyroid hormone metabolism and in detoxification

Expression profiling of human fetal cytosolic sulfotransferases involved in steroid and thyroid hormone metabolism and in detoxification
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DOI:
10.1016/j.mce.2005.06.003
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发表时间:
2005-08-30
影响因子:
4.1
通讯作者:
Coughtrie, MWH
Coughtrie, MWH
中科院分区:
医学2区
文献类型:
--
作者:
Stanley, EL;Hume, R;Coughtrie, MWH

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保护免受化学伤害对胎儿的正常发育至关重要,然而许多解毒酶在胎儿发育过程中表达不良。一个主要的例外是硫转移酶(SULT)家族,它似乎在发育中的人类中广泛表达。这些酶在许多激素的生物合成和体内平衡中也起着关键作用,包括雌激素和碘甲状腺原氨酸。因此,我们检测了各种人类胎儿和成人组织中SULT 1A、1B、1C、1E和2A家族的酶活性、蛋白质和mRNA表达。我们的研究结果表明,这些SULTs在人类胎儿中表达,其中大多数存在的水平相当于或高于成人。由于SULT1B1和1C2没有同种型选择性底物,我们使用免疫印迹分析首次显示SULT1B1在胎儿小肠中高水平表达,SULT1C2在胎儿肝脏、肾脏和小肠中表达。SULT1C2在成人肝脏和结肠中未表达。因此,硫转移酶在发育中的胎儿中的表达比在成人中的表达更为普遍,这对我们对人类发育生理学的理解具有重要意义。2005爱思唯尔爱尔兰有限公司版权所有。
Protection against chemical insult is essential for normal development of the fetus, however many detoxification enzymes are poorly expressed during fetal development. A major exception is the sulfotransferase (SULT) family, which appears to be widely expressed in the developing human. These enzymes also play a key role in biosynthesis and homeostasis of a number of hormones, including estrogens and iodothyronines. We therefore examined the enzyme activity, protein and mRNA expression of SULT 1A, 1B, 1C, 1E and 2A families in a variety of human fetal and adult tissues. Our results show that these SULTs are expressed in the human fetus, with most present at levels equivalent to or higher than the adult. As there are no isoform-selective substrates for SULTs 1B1 and 1C2 we used immunoblot analysis to show for the first time expression of SULT1B1 at high levels in fetal small intestine, and expression of SULT1C2 in fetal liver, kidney and small intestine. SULT1C2 was not expressed in adult liver or colon. Sulfotransferase expression in the developing fetus is therefore more widespread than in the adult, and this has significant implication for our understanding of human developmental physiology. (c) 2005 Elsevier Ireland Ltd. All rights reserved.