The goal of this paper is to explore the ability of the human female urogenital sinus immediately below the bladder (proximal urethra) to undergo prostatic development in response to dihydrotestosterone (DHT). To establish this idea, xenografts of human fetal female proximal urethra were grown in castrated nude mouse hosts receiving a subcutaneous DHT pellet. To verify the prostatic nature of the resultant glands, DHT-treated human fetal female urethral xenografts were compared with human fetal prostatic xenografts (derived from male specimens) grown in untreated and DHT-treated castrated mouse hosts and human fetal female proximal urethral xenografts grown in untreated castrated hosts. The resultant glands observed in DHT-treated human fetal female proximal urethral xenografts expressed 3 prostate-specific markers, NKX3.1, prostate specific antigen and prostatic acid phosphatase as well as the androgen receptor. Glands induced by DHT exhibited a protein expression profile of additional immunohistochemical markers (seven keratins, RUNX1, ESR2, TP63 and FOXA1) consistent with the unique spatial pattern of these proteins in prostatic ducts. Xenografts of human fetal female proximal urethra grown in DHT-treated hosts also expressed one of the salient features of prostatic development, namely androgen responsiveness. The experimental induction of prostatic differentiation from human fetal female proximal urethra makes possible future in-depth analysis of the molecular pathways directly involved in initiation of human prostatic development and subsequent epithelial differentiation, and more important whether the molecular pathways involved in human prostatic development are similar/identical versus different from that in murine prostatic development.

本文的目的是探讨紧邻膀胱下方的人类女性泌尿生殖窦（近尿道）响应二氢睾酮 (DHT) 进行前列腺发育的能力。为了证实这一想法，人类胎儿女性近端尿道的异种移植物在接受皮下 DHT 颗粒的去势裸鼠宿主中生长。为了验证所得腺体的前列腺性质，将经 DHT 处理的人胎儿女性尿道异种移植物与在未经处理和经 DHT 处理的去势小鼠宿主中生长的人胎儿前列腺异种移植物（源自男性标本）以及在未经治疗的阉割宿主。在 DHT 处理的人胎儿女性近端尿道异种移植物中观察到的腺体表达 3 种前列腺特异性标记物：NKX3.1、前列腺特异性抗原和前列腺酸性磷酸酶以及雄激素受体。DHT 诱导的腺体表现出额外免疫组织化学标记物（七个角蛋白、RUNX1、ESR2、TP63 和 FOXA1）的蛋白质表达谱，与前列腺管中这些蛋白质的独特空间模式一致。在 DHT 处理的宿主中生长的人类胎儿女性近端尿道异种移植物也表达了前列腺发育的显着特征之一，即雄激素反应性。人类胎儿女性近端尿道前列腺分化的实验诱导，使得未来深入分析直接参与人类前列腺发育起始和随后的上皮分化的分子途径成为可能，更重要的是参与人类前列腺发育的分子途径是否相似/与小鼠前列腺发育中的相同与不同。