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引用次数: 0
摘要
哺乳动物细胞膜磺基转移酶(SULTs)催化内分泌激素以及大量药物、环境化学物质和其他异种生物的硫化反应。许多干扰内分泌的化学物质(EDCs)作为底物和抑制剂与这些 SULTs 相互作用,从而改变了负责代谢和调节雌激素和甲状腺激素等内分泌激素的硫化反应。EDCs 或其代谢物还可能通过与核受体和其他转录因子的直接相互作用来调节 SULTs 的表达。此外,由 EDC 衍生出的一些硫酸酯(EDC-硫酸盐)可作为内分泌激素受体的配体。虽然 EDC 的硫酸盐化会导致其随尿液或胆汁排出体外,但它也可能通过与血清蛋白的可逆性结合而导致 EDC-硫酸盐的保留,从而使其转运到其他组织进行细胞内水解,进而干扰内分泌。本微型综述概述了 SULTs 和硫酸化作用在 EDC 影响中的潜在作用,以及我们对这些过程不断发展的认识。
Cytosolic sulfotransferases in endocrine disruption.
The mammalian cytosolic sulfotransferases (SULTs) catalyze the sulfation of endocrine hormones as well as a broad array of drugs, environmental chemicals, and other xenobiotics. Many endocrine-disrupting chemicals (EDCs) interact with these SULTs as substrates and inhibitors, and thereby alter sulfation reactions responsible for metabolism and regulation of endocrine hormones such as estrogens and thyroid hormones. EDCs or their metabolites may also regulate expression of SULTs through direct interaction with nuclear receptors and other transcription factors. Moreover, some sulfate esters derived from EDCs (EDC-sulfates) may serve as ligands for endocrine hormone receptors. While the sulfation of an EDC can lead to its excretion in the urine or bile, it may also result in retention of the EDC-sulfate through its reversible binding to serum proteins and thereby enable transport to other tissues for intracellular hydrolysis and subsequent endocrine disruption. This mini-review outlines the potential roles of SULTs and sulfation in the effects of EDCs and our evolving understanding of these processes.
期刊介绍:
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