Sulfation of tibolone and tibolone metabolites by expressed human cytosolic sulfotransferases
Sulfation of tibolone and tibolone metabolites by expressed human cytosolic sulfotransferases
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DOI：
10.1016/j.jsbmb.2004.01.005
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发表时间：
2004-04-01
影响因子：
4.1
通讯作者：
Falany, CN
中科院分区：
文献类型：
--
作者：
Falany, JL;Macrina, N;Falany, CN
替勃龙是许多国家用于治疗更年期症状的重要治疗药物，对更年期和绝经后血管舒缩、骨骼、阴道和情绪症状具有有益作用，而不影响子宫内膜、乳房或心血管系统。替勃龙快速代谢为活性代谢物（包括 3α-OH-替勃龙、3β-OH-替勃龙和 Delta(4)-替勃龙）可能对其组织特异性作用很重要。硫酸化在替勃龙及其代谢物的代谢和组织特异性活性的调节中也具有重要作用。检查了七种主要表达的人磺基转移酶 (SULT) 亚型硫酸化替勃龙及其三种代谢物的能力。表达的人 SULT2A1 能够硫酸化替勃龙以及对 3a-OH-替勃龙具有最高亲和力的所有三种代谢物。 SULT1E1 与 3-OH-替勃龙代谢物和替勃龙本身轻微缀合。 SULT2B1b 硫酸化两种 3-OH 代谢物，但不硫酸化替勃龙或 Delta(4)-替勃龙。 SULT 亚型 1A1、1A3、1B1 和 1C1 未表现出可检测的活性。分析替勃龙及其代谢物被人体组织胞质溶胶的硫酸化，以确定替勃龙硫酸化模式是否与每个组织中 SULT 亚型的已知表达相对应。替勃龙的组织特异性作用可能部分是通过特定的人 SULT 异构体使替勃龙及其代谢物失活来调节的。 (C) 2004 Elsevier Ltd. 保留所有权利。
Tibolone is an important therapeutic agent used in the treatment of menopausal symptoms in many countries and has beneficial effects on menopausal and postmenopausal vasomotor, bone, vaginal and mood symptoms without affecting the endometrial, breast or cardiovascular systems. The rapid metabolism of tibolone to active metabolites including 3alpha-OH-tibolone, 3beta-OH-tibolone and Delta(4)-tibolone may be important in its tissue-specific effects. Sulfation also has a major role in the metabolism and regulation of the tissue-specific activity of tibolone and its metabolites. The ability of seven major expressed human sulfotransferase (SULT) isoforms to sulfate tibolone and its three metabolites was examined. Expressed human SULT2A1 was capable of sulfating tibolone and all three metabolites with the highest affinity for 3a-OH-tibolone. SULT1E1 conjugated both 3-OH-tibolone metabolites and tibolone itself slightly. SULT2B1b sulfated both 3-OH metabolites but not tibolone or Delta(4)-tibolone. SULT isoforms 1A1, 1A3, 1B1 and 1C1 did not demonstrate detectable activity. Sulfation of tibolone and its metabolites by human tissue cytosols was analyzed to determine whether the pattern of tibolone sulfation corresponded to the known expression of SULT isoforms in each tissue. The tissue-specific effects of tibolone may be regulated in part by the inactivation of tibolone and its metabolites by specific human SULT isoforms. (C) 2004 Elsevier Ltd. All rights reserved.