Kim Kun Suk, Liu Wenhui, Cunha Gerald R, Russell David W, Huang Hongying, Shapiro Ellen, Baskin Laurence S
Department of Urology, University of California, San Francisco, San Francisco, California 94143, USA.
Cell Tissue Res. 2002 Feb;307(2):145-53. doi: 10.1007/s004410100464. Epub 2001 Nov 27.
Normal penile development is dependent on testosterone, its conversion via steroid 5 alpha-reductase type 2 to dihydrotestosterone, and a functional androgen receptor (AR). The goal of this study was to investigate the distribution of AR and 5 alpha-reductase type 2 in the developing human fetal external genitalia with special emphasis on urethra formation. Twenty fetal genital specimens from normal human males (12-20 weeks gestation) were sectioned serially and stained by avidin-biotinylated peroxidase complex method with antigen retrieval. Stained sections throughout male genital development documented the expression of AR and 5 alpha-reductase type 2 in the phallus. Between 12 and 14 weeks of gestation, AR was localized to epithelial cells of the urethral plate in the glans, the tubular urethra of the penile shaft, and stromal tissue surrounding the urethral epithelium. In the fetal penis between 16 and 20 weeks gestation, the density of AR expression was greatest in urethral epithelial cells versus the surrounding stromal tissues. There was a characteristic pattern of AR expression in the glandular urethral epithelium between 16 and 20 weeks gestation. AR expression was greater along the ventral aspect of the glandular urethra than along the dorsal aspect of the urethral epithelium. The expression of 5 alpha-reductase type 2 was localized to the stroma surrounding the urethra, especially along the urethral seam area in the ventral portion of the remodeling urethra. These anatomical studies support the hypothesis that androgens are essential for the formation of the ventral portion of the urethra and that abnormalities in either the AR or 5 alpha-reductase type 2 can explain the occurrence of hypospadias.
正常阴茎发育依赖于睾酮、其通过2型类固醇5α-还原酶转化为双氢睾酮以及功能性雄激素受体（AR）。本研究的目的是调查AR和2型5α-还原酶在发育中的人类胎儿外生殖器中的分布，特别关注尿道形成。对20例来自正常男性胎儿（妊娠12 - 20周）的生殖器标本进行连续切片，并采用抗生物素蛋白-生物素化过氧化物酶复合物法进行染色，同时进行抗原修复。整个男性生殖器发育过程中的染色切片记录了AR和2型5α-还原酶在阴茎中的表达情况。在妊娠12至14周之间，AR定位于龟头尿道板的上皮细胞、阴茎体部的管状尿道以及尿道上皮周围的间质组织。在妊娠16至20周的胎儿阴茎中，与周围间质组织相比，AR在尿道上皮细胞中的表达密度最高。在妊娠16至20周之间，腺性尿道上皮中存在AR表达的特征性模式。腺性尿道腹侧的AR表达高于尿道上皮背侧。2型5α-还原酶的表达定位于尿道周围的间质，尤其是在重塑尿道腹侧部分的尿道缝区域。这些解剖学研究支持了以下假说：雄激素对于尿道腹侧部分的形成至关重要，并且AR或2型5α-还原酶的异常可以解释尿道下裂的发生。
