Berman D M, Tian H, Russell D W
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235-9046, USA.
Mol Endocrinol. 1995 Nov;9(11):1561-70. doi: 10.1210/mend.9.11.8584033.
Two androgens, testosterone and dihydrotestosterone, are required for the development of the male urogenital tract in the rat. Testosterone is secreted by the fetal testes and is thought to elicit differentiation of the Wolffian ducts into seminal vesicles, vas deferens, and epididymides. Testosterone is converted into dihydrotestosterone by steroid 5 alpha-reductase in the urogenital tract, and this conversion is necessary for the differentiation of the prostate and external genitalia. Genes encoding two 5 alpha-reductase isozymes, designated type 1 and type 2, have been identified. We examined the expression and regulation of these genes on days 17-21 in the urogenital tracts of male and female fetuses. Expression of the type 1 gene predominated in epithelial cells, whereas type 2 gene expression was limited to mesenchymal cells. Surprisingly, this expression pattern was detected in both testosterone-dependent and dihydrotestosterone-dependent anlagen of the urogenital tract and was the same in both male and female fetuses. Furthermore, transcripts encoding the two isozymes were present in their respective cell types before the overt differentiation of internal genitalia. Androgens stimulated expression of the type 2 gene in the urogenital tracts of both sexes, but did not effect expression of the type 1 gene or the cell type-specific expression patterns of the 5 alpha-reductase genes. In the adult prostate, 5 alpha-reductase gene expression is under feedforward control, in which the product of the enzyme, dihydrotestosterone, stimulates the expression of the gene. However, no evidence for feedforward regulation of either 5 alpha-reductase gene was detected in the fetus.
两种雄激素，睾酮和双氢睾酮，是大鼠雄性泌尿生殖道发育所必需的。睾酮由胎儿睾丸分泌，被认为可促使中肾管分化为精囊、输精管和附睾。睾酮在泌尿生殖道中被类固醇5α-还原酶转化为双氢睾酮，这种转化对于前列腺和外生殖器的分化是必需的。已鉴定出编码两种5α-还原酶同工酶（分别称为1型和2型）的基因。我们研究了这些基因在雄性和雌性胎儿泌尿生殖道发育第17至21天的表达和调控情况。1型基因的表达在上皮细胞中占主导，而2型基因的表达仅限于间充质细胞。令人惊讶的是，在泌尿生殖道中依赖睾酮和依赖双氢睾酮的原基中均检测到这种表达模式，并且在雄性和雌性胎儿中都是相同的。此外，在内部生殖器明显分化之前，编码这两种同工酶的转录本就在各自的细胞类型中存在。雄激素刺激了两性泌尿生殖道中2型基因的表达，但不影响1型基因的表达或5α-还原酶基因的细胞类型特异性表达模式。在成年前列腺中，5α-还原酶基因表达受前馈控制，即该酶的产物双氢睾酮刺激该基因的表达。然而，在胎儿中未检测到任何一种5α-还原酶基因存在前馈调节的证据。
