DELETION OF STEROID 5-ALPHA-REDUCTASE 2-GENE IN MALE PSEUDOHERMAPHRODITISM
DELETION OF STEROID 5-ALPHA-REDUCTASE 2-GENE IN MALE PSEUDOHERMAPHRODITISM
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DOI：
10.1038/354159a0
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发表时间：
1991-11-14
期刊：
影响因子：
64.8
通讯作者：
RUSSELL, DW
中科院分区：
文献类型：
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作者：
ANDERSSON, S;BERMAN, DM;RUSSELL, DW
睾酮在类固醇5-α-还原酶的作用下转化为二氢睾酮是雄激素作用中的一个关键反应，对胚胎发育过程中男性表型的形成和雄激素介导的组织生长都是必不可少的，例如破坏这种转化的前列腺单基因缺陷会导致假两性畸形，即46X，Y男性有男性内生殖道，而女性外生殖器3。我们描述了从前列腺中分离出一个人类5-α-还原酶互补DNA。随后的克隆和遗传学研究表明，该基因(命名为5-α-还原酶1)在5-α-还原酶缺乏症患者中是正常的。在这里，我们报告了通过表达克隆和聚合酶链式反应分离到第二个5-α-还原酶基因。该基因编码的酶(命名为5-α-还原酶2)的生化和药理性质与它是生殖器组织中的主要同工酶一致。在两个由5-α-还原酶缺乏引起的男性假两性畸形的相关个体中，存在该基因的缺失。这些结果证实了男性中至少存在两种5-α-还原酶，并提供了对男性性别分化中由激素介导的基本事件的洞察。
THE conversion of testosterone into dihydrotestosterone by steroid 5-alpha-reductase is a key reaction in androgen action, and is essential both for the formation of the male phenotype during embryogenesis and for androgen-mediated growth of tissues such as the prostate Single gene defects that impair this conversion lead to pseudohermaphroditism in which 46 X, Y males have male internal urogenital tracts, but female external genitalia 3. We have described the isolation of a human 5-alpha-reductase complementary DNA from prostate . Subsequent cloning and genetic studies showed that this gene (designated 5-alpha-reductase 1) was normal in patients with 5-alpha-reductase deficiency 26. We report here the isolation of a second 5-alpha-reductase cDNA by expression cloning and the polymerase chain reaction. The biochemical and pharmacological properties of this cDNA-encoded enzyme (designated 5-alpha-reductase 2) are consistent with it being the major isozyme in genital tissue. A deletion in this gene is present in two related individuals with male pseudohermaphroditism caused by 5-alpha-reductase deficiency. These results verify the existence of at least two 5-alpha-reductases in man and provide insight into a fundamental hormone-mediated event in male sexual differentiation.