Characteristics of human types 1, 2 and 3 17 beta-hydroxysteroid dehydrogenase activities: Oxidation reduction and inhibition
Characteristics of human types 1, 2 and 3 17 beta-hydroxysteroid dehydrogenase activities: Oxidation reduction and inhibition
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DOI：
10.1016/0960-0760(95)00209-x
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发表时间：
1995-12-01
影响因子：
4.1
通讯作者：
Labrie, F
中科院分区：
文献类型：
--
作者：
LuuThe, V;Zhang, Y;Labrie, F
在将1型、2型和3型17 β-羟基类固醇脱氢酶（17 β-HSD）cDNA转染到转化的胚肾（293）细胞中后，我们表征了这些活性的选择性定向和抑制特性。虽然转染细胞的匀浆可以催化底物和产物的相互转化，但与对这些酶活性的普遍看法一致，为了更好地反映生理条件，在完整细胞中测量的相同活性显示出单向反应。1型和3型17 β-HSD分别催化雌酮还原为雌二醇和LC-雄烯二酮还原为睾酮，而2型17 β-HSD分别催化睾酮和17 β-雌二醇氧化转化为4-雄烯二酮和雌酮。另外，1型、2型和3型17 β-HSD活性的最适pH值不同。类型1和类型3分别显示出以5和6左右为中心的pH最佳值，而类型2的17 β-HSD活性（其优先催化氧化反应）在碱性pH（8-10）下具有更高的活性。还观察到最佳孵育温度的差异：1型17 β-HSD显示出相对较高的温度耐受性（55 ℃）。相比之下，2型和3型在37摄氏度时功能最佳。类型1、2和3的17 β-HSD活性也可以通过它们对各种特异性抑制剂的敏感性来区分：类型1被在位置16 α处含有溴/或碘丙基的雌二醇衍生物强力抑制。另一方面，在17位含有螺-γ-内酯的雌酮衍生物对2型17 β-HSD显示出有效的抑制作用，而3型则被1，4-雄甾二烯-1，6，17-三酮强烈抑制。
Following transfection of types 1, 2 and 3 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) cDNAs into transformed embryonal kidney (293) cells, we have characterized the selective directional and inhibitory characteristics of these activities. While homogenates of transfected cells could catalyze interconversion of the substrate and product, in agreement with the general belief on the activity of these enzymes, the same activities measured in intact cells, in order to better reflect the physiological conditions, showed an unidirectional reaction. Types 1 and 3 17 beta-HSD catalyzed the reduction of estrone to estradiol and LC-androstenedione to testosterone, respectively, while type 2 17 beta-HSD catalyzed the oxidative transformation of both testosterone and 17 beta-estradiol to 4-androstenedione and estrone, respectively. In addition, types 1, 2 and 3 17 beta-HSD activities showed different pH optima. While types 1 and 3 showed pH optimum values centered at around 5 and 6, respectively, type 2 17 beta-HSD activity, which preferentially catalyzes the oxidation reaction, has higher activity at an alkaline pH (8-10). Differences in the optimum incubation temperatures were also observed: type 1 17 beta-HSD shows a relatively high temperature tolerance (55 degrees C). In contrast, type 2 and 3 functioned best at 37 degrees C. Types 1, 2 and 3 17 beta-HSD activities could be also differentiated by their sensitivity toward various specific inhibitors: type 1 was potently inhibited by an estradiol derivative containing a bromo/or iodopropyl group at position 16 alpha. On the other hand a derivative of estrone containing a spiro-gamma-lactone at position 17 showed a potent inhibitory effect on type 2 17 beta-HSD, whereas type 3 was strongly inhibited by 1,4-androstadiene-1,6,17-trione.