Abstract:
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.
摘要:
哺乳动物胞质磺基转移酶(SULTs)催化内分泌激素的硫酸化以及广泛的药物,环境化学品,和其他外源性物质。许多内分泌干扰化学物质(EDCs)与这些SULTs作为底物和抑制剂相互作用,从而改变负责代谢和调节内分泌激素如雌激素和甲状腺激素的硫酸化反应。EDC或其代谢物还可以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,一些来源于EDC的硫酸酯(EDC-硫酸盐)可作为内分泌激素受体的配体。虽然EDC的硫酸化可导致其在尿液或胆汁中排泄,它还可以通过其与血清蛋白的可逆结合而导致EDC-硫酸盐的保留,从而能够运输到其他组织用于细胞内水解和随后的内分泌破坏。这篇小型综述概述了SULTs和硫酸化在EDCs影响中的潜在作用,以及我们对这些过程的不断发展的理解。