Penning T M, Smithgall T E, Askonas L J, Sharp R B
Steroids. 1986 Apr-May;47(4-5):221-47. doi: 10.1016/0039-128x(86)90094-2.
3 alpha-HSD appears to be a multifunctional enzyme. In addition to its traditional role of catalyzing early steps in androgen metabolism, it will also oxidoreduce prostaglandins and detoxify trans-dihydrodiols (proximate carcinogens). Since these novel reactions have been quantified using homogeneous enzyme it is necessary to interpret the role of the enzyme in these processes in vivo with some caution. However, it is rare that such observations on a purified hydroxysteroid dehydrogenase have led to such important questions. Is the 3 alpha-HSD the only steroid dehydrogenase that transforms prostaglandins and trans-dihydrodiols? Are hydroxysteroid dehydrogenases and prostaglandin dehydrogenases the same enzymes in certain tissues? Does 3 alpha-HSD protect against chemical carcinogenesis in vivo? The inhibition of the purified dehydrogenase by therapeutically relevant concentrations of anti-inflammatory drugs also deserves comment. Is this hydroxysteroid dehydrogenase really an in vivo target for anti-inflammatory drug action? Could these drugs exert some of their pharmacological effect either by preventing glucocorticoid metabolism in some tissues or by preventing the transformation of PGF2 alpha (non-inflammatory prostanoid) to PGE2 (a pro-inflammatory prostanoid)? Could these drugs, by inhibiting trans-dihydrodiol oxidation, potentiate the initiation of chemical carcinogenesis? These and other important questions can be answered only by developing specific inhibitors for the dehydrogenase to decipher its function in vivo.
3α-羟基类固醇脱氢酶似乎是一种多功能酶。除了其催化雄激素代谢早期步骤的传统作用外，它还能氧化还原前列腺素并使反式二氢二醇（近似致癌物）解毒。由于这些新反应已使用均一酶进行了定量，因此有必要谨慎解释该酶在体内这些过程中的作用。然而，对纯化的羟基类固醇脱氢酶的此类观察很少引发如此重要的问题。3α-羟基类固醇脱氢酶是唯一能转化前列腺素和反式二氢二醇的类固醇脱氢酶吗？在某些组织中，羟基类固醇脱氢酶和前列腺素脱氢酶是同一种酶吗？3α-羟基类固醇脱氢酶在体内能预防化学致癌作用吗？治疗相关浓度的抗炎药对纯化脱氢酶的抑制作用也值得关注。这种羟基类固醇脱氢酶真的是抗炎药作用的体内靶点吗？这些药物是否可以通过阻止某些组织中的糖皮质激素代谢或阻止PGF2α（非炎性前列腺素）转化为PGE2（炎性前列腺素）来发挥其部分药理作用？这些药物通过抑制反式二氢二醇氧化，会增强化学致癌作用的起始吗？只有开发出该脱氢酶的特异性抑制剂以阐明其在体内的功能，才能回答这些及其他重要问题。
