STRUCTURAL AND BIOCHEMICAL-PROPERTIES OF CLONED AND EXPRESSED HUMAN AND RAT STEROID 5-ALPHA-REDUCTASES
STRUCTURAL AND BIOCHEMICAL-PROPERTIES OF CLONED AND EXPRESSED HUMAN AND RAT STEROID 5-ALPHA-REDUCTASES
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DOI：
10.1073/pnas.87.10.3640
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发表时间：
1990-05-01
影响因子：
11.1
通讯作者：
RUSSELL, DW
中科院分区：
文献类型：
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作者：
ANDERSSON, S;RUSSELL, DW
微粒体酶类固醇5 α-还原酶负责将睾酮转化为更有效的雄激素二氢睾酮。在人类中，这种类固醇作用于各种雄激素反应靶组织，以介导多种内分泌过程，如胎儿的男性性别分化和男性的前列腺生长。在此，我们描述了编码人类固醇5 α的cDNA的分离、结构和表达。还原酶的活性。以大鼠前列腺cDNA为探针，筛选人前列腺cDNA文库。鉴定了2.1-脱氢酶cDNA，DNA序列分析表明，人类固醇5 α-脱氢酶cDNA与人类固醇5 α-脱氢酶cDNA相同。还原酶是259个氨基酸的疏水蛋白，预测分子量为29，462。人类和大鼠蛋白质序列的比较显示了60%的同一性。将含有人和大鼠cDNA的表达载体转染到猿COS细胞中导致高水平的类固醇5 α-β-D的合成。还原酶活性COS细胞中表达的两种酶对天然存在的类固醇激素表现出相似的底物特异性。然而，合成的4-氮杂甾类化合物在抑制人和大鼠类固醇5 α-雌二醇的能力上表现出显著的差异。还原酶
The microsomal enzyme steroid 5.alpha.-reductase is responsible for the conversion of testosterone into the more potent androgen dihydrotestosterone. In man, this steroid acts on a variety of androgen-responsive target tissues to mediate such diverse endocrine processes as male sexual differentiation in the fetus and prostatic growth in men. Here we describe the isolation, structure, and expression of a cDNA encoding the human steroid 5.alpha.-reductase. A rat cDNA was used as a hybridization probe to screen a human prostate cDNA library. A 2.1-kilobase cDNA was identified and DNA sequence analysis indicated that the human steroid 5.alpha.-reductase was a hydrophobic protein of 259 amino acids with a predicted molecular weight of 29,462. A comparison of the human and rat protein sequences revealed a 60% identity. Transfection of expression vectors containing the human and rat cDNAs into simian COS cells resulted in the synthesis of high levels of steroid 5.alpha.-reductase enzyme activity. Both enzymes expressed in COS cells showed similar substrate specificities for naturally occurring steroid hormones. However, synthetic 4-azasteroids demonstrated and marked differences in their abilities to inhibit the human and rat steroid 5.alpha.-reductases.