Visser T J, Kaptein E, Glatt H, Bartsch I, Hagen M, Coughtrie M W
Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands.
Chem Biol Interact. 1998 Feb 20;109(1-3):279-91. doi: 10.1016/s0009-2797(97)00139-7.
Sulfation is an intriguing pathway of thyroid hormone metabolism since it facilitates the degradation of the hormone by the type I deiodinase (D1). This study reports the preliminary characterization of iodothyronine sulfotransferase activities of rat and human liver cytosol and recombinant rSULT1C1 and hSULT1A1 isoenzymes. All these enzyme preparations catalyzed the sulfation of--in decreasing order of efficiency--3,3'-diiodothyronine (3,3'-T2) > 3,3',5-triiodothyronine (T3) approximately 3,3',5'-triiodothyronine (rT3) > thyroxine (T4). 3,3'-T2 sulfotransferase activity was found to be higher in male than in female rat liver, which has also been shown by others for the expression of rSULT1A1 and rSULT1C1. No sulfation of iodothyronines was observed with rSULT1A1. Different phenol derivatives were found to be potent inhibitors of the sulfation of 3,3'-T2 by native and recombinant sulfotransferases, with pentachlorophenol and 2,4,6-tribromophenol being the most potent. The inhibitions exerted by the different phenols on 3,3'-T2 sulfation by rSULT1C1 correlated better with the effects observed in male than with those in female liver. A strong correlation was also observed between the inhibition profiles of human liver cytosol and hSUL1T1A1. These results suggest that: (1) rSULT1C1 is an important isoenzyme for the sulfation of thyroid hormone in male rat liver; (2) another isoenzyme with similar properties, perhaps rSULT1B1, is responsible for thyroid hormone sulfation in female rat liver and may also contribute to this process in male rat liver; and (3) hSULT1A1 is an important isoenzyme for thyroid hormone sulfation in human liver.
硫酸化是甲状腺激素代谢中一条引人关注的途径，因为它可通过I型脱碘酶（D1）促进甲状腺激素的降解。本研究报告了大鼠和人肝脏胞浆以及重组rSULT1C1和hSULT1A1同工酶的碘甲状腺原氨酸硫酸转移酶活性的初步特征。所有这些酶制剂都催化硫酸化反应，效率由高到低依次为：3,3'-二碘甲状腺原氨酸（3,3'-T2）> 3,3',5-三碘甲状腺原氨酸（T3）≈ 3,3',5'-三碘甲状腺原氨酸（rT3）> 甲状腺素（T4）。发现雄性大鼠肝脏中的3,3'-T2硫酸转移酶活性高于雌性大鼠肝脏，其他人对rSULT1A1和rSULT1C1表达的研究也表明了这一点。rSULT1A1未观察到碘甲状腺原氨酸的硫酸化作用。发现不同的酚类衍生物是天然和重组硫酸转移酶对3,3'-T2硫酸化的有效抑制剂，其中五氯酚和2,4,6-三溴酚的抑制作用最强。不同酚类对rSULT1C1催化的3,3'-T2硫酸化的抑制作用与雄性大鼠肝脏中观察到的效应相关性更好，而与雌性大鼠肝脏中的效应相关性较差。人肝脏胞浆和hSUL1T1A1的抑制谱之间也观察到很强的相关性。这些结果表明：（1）rSULT1C1是雄性大鼠肝脏中甲状腺激素硫酸化的重要同工酶；（2）另一种具有相似性质的同工酶，可能是rSULT1B1，负责雌性大鼠肝脏中甲状腺激素的硫酸化，也可能在雄性大鼠肝脏的这一过程中起作用；（3）hSULT1A1是人类肝脏中甲状腺激素硫酸化的重要同工酶。
