Department of Urology, University of California, 400 Parnassus Avenue, San Francisco, CA, 94143, USA.
Department of Urology, University of California, 400 Parnassus Avenue, San Francisco, CA, 94143, USA.
Differentiation. 2020 Sep-Oct;115:37-52. doi: 10.1016/j.diff.2020.06.001. Epub 2020 Jul 14.
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.
本文旨在探讨女性膀胱下方的泌尿生殖窦（近端尿道）在接受二氢睾酮（DHT）刺激后能否发育为前列腺。为了验证这一观点，我们将人胎儿近端尿道的异种移植物植入接受皮下 DHT 植入物的去势裸鼠体内。为了验证所得腺体的前列腺特性，我们将 DHT 处理的人胎儿女性尿道异种移植物与未处理和 DHT 处理的去势鼠宿主中生长的人胎儿前列腺异种移植物（源自男性标本）以及未处理的去势宿主中生长的人胎儿女性近端尿道异种移植物进行了比较。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了 3 种前列腺特异性标志物，即 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的免疫组织化学标志物（7 种角蛋白、RUNX1、ESR2、TP63 和 FOXA1）的蛋白表达谱，与这些蛋白质在前列腺导管中的独特空间模式一致。在 DHT 处理的宿主中生长的人胎儿女性近端尿道异种移植物也表达了前列腺发育的一个显著特征，即雄激素反应性。从人胎儿女性近端尿道诱导前列腺分化的实验为深入分析直接参与人类前列腺发育和随后的上皮分化的分子途径提供了可能，更重要的是，参与人类前列腺发育的分子途径是否与小鼠前列腺发育的途径相似/相同或不同。
