Shapiro Ellen, Huang Hongying, Masch Rachel J, McFadden Deborah E, Wu Xue-Ru, Ostrer Harry
Department of Urology, New York University School of Medicine, New York, New York 10016, USA.
J Urol. 2005 Oct;174(4 Pt 2):1695-8; discussion 1698. doi: 10.1097/01.ju.0000179540.28209.de.
Expression and cellular localization of the androgen receptor (AR) and estrogen receptor (ER) isoforms were determined using antibodies specific to these receptors and to specific cell types.
Gonads and genitourinary structures were removed from 5 human male fetuses 7 to 22 weeks of gestational age. Sections were stained with antibodies to AR, ERalpha and ERbeta, P450 scc and smooth muscle actin.
AR was present in undifferentiated gonadal cells, peritubular myoid cells and in some Leydig and stromal cells at 7 weeks of gestation. The number of AR positive peritubular myoid cells remained constant through 22 weeks of gestation but the number of AR positive stromal cells continued to increase through 22 weeks. ERalpha was apparent by 12 weeks of gestation with perinuclear staining of Leydig cells, peaked at 16 weeks and then diminished. ERbeta was first observed at 7 weeks in undifferentiated gonadal cells. By 12 weeks of gestation ERbeta was apparent in germ cells, PTMC and Leydig cells. In the epididymis AR was expressed in the epithelium and stroma of the efferent ductules and the ductus epididymis by 7 weeks of gestation with increased expression by 12 weeks. A similar pattern of staining was observed for ERbeta. By contrast, staining of ERalpha was observed only in the epithelium of the epididymis from 7 weeks of gestation onward with no apparent ERalpha staining in the tail of the epididymis.
These findings are compatible with the well-known roles of androgen signaling in sexual differentiation and spermatogenesis in humans. The role of estrogens in the developing human testis and epididymis remains unknown.
使用针对这些受体及特定细胞类型的特异性抗体,确定雄激素受体(AR)和雌激素受体(ER)亚型的表达及细胞定位。
从5例孕龄7至22周的人类男性胎儿中取出性腺和泌尿生殖结构。切片用抗AR、ERα、ERβ、P450 scc和平滑肌肌动蛋白的抗体进行染色。
妊娠7周时,AR存在于未分化的性腺细胞、睾丸白膜肌样细胞以及一些睾丸间质细胞和支持细胞中。妊娠22周内,AR阳性的睾丸白膜肌样细胞数量保持恒定,但AR阳性的间质细胞数量在22周内持续增加。ERα在妊娠12周时可见,在睾丸间质细胞中呈核周染色,16周时达到峰值,随后减少。ERβ在妊娠7周时首次在未分化的性腺细胞中被观察到。到妊娠12周时,ERβ在生殖细胞、睾丸白膜肌样细胞和睾丸间质细胞中明显可见。在附睾中,妊娠7周时AR在输出小管和附睾管的上皮和间质中表达,12周时表达增加。ERβ也观察到类似的染色模式。相比之下,从妊娠7周起,仅在附睾上皮中观察到ERα染色,附睾尾部未观察到明显的ERα染色。
这些发现与雄激素信号在人类性别分化和精子发生中的已知作用相符。雌激素在发育中的人类睾丸和附睾中的作用尚不清楚。