Berman D M, Russell D W
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9359-63. doi: 10.1073/pnas.90.20.9359.
The enzyme steroid 5 alpha-reductase (EC 1.3.99.5) is a component of an intercellular signaling pathway that determines cell fate in the primordium of the mammalian reproductive tract. During male phenotypic sexual differentiation, the dihydrotestosterone product of this enzyme binds to the androgen receptor and initiates development of the external genitalia and prostate. Genes encoding two isozymes of steroid 5 alpha-reductase with different biochemical properties and tissue distributions have recently been isolated. In the current study, we utilize in situ hybridization analysis to determine cell-type-specific expression patterns of the 5 alpha-reductase isozyme mRNAs in two androgen target tissues (regenerating ventral prostate and epididymis) and a peripheral tissue (liver). In regenerating ventral prostate, the type 1 mRNA is expressed in basal epithelial cells whereas expression of the type 2 mRNA is largely confined to stromal cells. These results were confirmed by immunohistochemical analysis and are consistent with distinct roles played by the isozymes in the prostate. In the epididymis, both 5 alpha-reductase isozyme mRNAs are expressed in epithelial cells. Only the type 1 mRNA is present in the liver. This mRNA is distributed in a striking spatial gradient extending from hepatocytes surrounding the portal triad (high expression) to those surrounding the central vein (low to absent expression). These findings demonstrate cell-type-specific expression of the steroid 5 alpha-reductase isozymes and underscore their distinct and overlapping functions in androgen physiology.
类固醇5α-还原酶（EC 1.3.99.5）是一种细胞间信号通路的组成部分，该信号通路决定哺乳动物生殖道原基中的细胞命运。在雄性表型性分化过程中，这种酶产生的二氢睾酮与雄激素受体结合，并启动外生殖器和前列腺的发育。最近已分离出编码具有不同生化特性和组织分布的两种类固醇5α-还原酶同工酶的基因。在本研究中，我们利用原位杂交分析来确定5α-还原酶同工酶mRNA在两种雄激素靶组织（再生腹侧前列腺和附睾）和一种外周组织（肝脏）中的细胞类型特异性表达模式。在再生腹侧前列腺中，1型mRNA在基底上皮细胞中表达，而2型mRNA的表达主要局限于基质细胞。这些结果通过免疫组织化学分析得到证实，并且与同工酶在前列腺中发挥的不同作用一致。在附睾中，两种5α-还原酶同工酶mRNA均在上皮细胞中表达。肝脏中仅存在1型mRNA。这种mRNA以显著的空间梯度分布，从围绕门三联管的肝细胞（高表达）延伸至围绕中央静脉的肝细胞（低表达至无表达）。这些发现证明了类固醇5α-还原酶同工酶的细胞类型特异性表达，并强调了它们在雄激素生理学中的不同和重叠功能。
