GENETIC AND PHARMACOLOGICAL EVIDENCE FOR MORE THAN ONE HUMAN STEROID 5-ALPHA-REDUCTASE
GENETIC AND PHARMACOLOGICAL EVIDENCE FOR MORE THAN ONE HUMAN STEROID 5-ALPHA-REDUCTASE
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DOI：
10.1172/jci115574
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发表时间：
1992-01-01
影响因子：
15.9
通讯作者：
RUSSELL, DW
中科院分区：
文献类型：
--
作者：
JENKINS, EP;ANDERSSON, S;RUSSELL, DW
类固醇5-α-还原酶催化睾酮转化为更有效的雄激素--双氢睾酮，这种反应的障碍会导致一种男性假两性畸形，在这种情况下，遗传男性主要分化为表型女性。我们之前分离了编码人类类固醇5-α-还原酶的cdna克隆。在这里，我们报告了分子和遗传学研究表明，在遗传性疾病类固醇5-α还原酶缺乏的受试者中，编码这种cdna的基因是正常的。我们进一步表明，与前列腺和培养的皮肤成纤维细胞中的主要类固醇5-α-还原酶相比，该基因编码的酶表现出中性到碱性的最适pH，并且对4-氮杂类固醇，非那雄胺(MK-906)的抑制作用不那么敏感。这些结果为人类中存在至少两种类固醇5-α-还原酶同工酶提供了遗传、生化和药理学支持。
The enzyme steroid 5-alpha-reductase catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone, and impairment of this reaction causes a form of male pseudohermaphroditism in which genetic males differentiate predominantly as phenotypic females. We previously isolated cDNA clones that encode a human steroid 5-alpha-reductase enzyme. Here, we report molecular and genetic studies demonstrating that the gene encoding this cDNA is normal in subjects with the genetic disease steroid 5-alpha-reductase deficiency. We further show that in contrast to the major steroid 5-alpha-reductase in the prostate and cultured skin fibroblasts, the cDNA-encoded enzyme exhibits a neutral to basic pH optima and is much less sensitive to inhibition by the 4-aza steroid, finasteride (MK-906). The results provide genetic, biochemical, and pharmacological support for the existence of at least two steroid 5-alpha-reductase isozymes in man.