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Regulation of masculinization: androgen signalling for external genitalia development
Nature Reviews Urology ( IF 12.1 ) Pub Date : 2018-04-18 , DOI: 10.1038/s41585-018-0008-y
Shoko Matsushita , Kentaro Suzuki , Aki Murashima , Daiki Kajioka , Alvin Resultay Acebedo , Shinichi Miyagawa , Ryuma Haraguchi , Yukiko Ogino , Gen Yamada

The biology of masculinization is fundamentally important for understanding the embryonic developmental processes that are involved in the development of the male reproductive tract, external genitalia, and also the tumorigenesis of prostate cancer. The molecular mechanisms of masculinization are of interest to many researchers and clinicians involved in varied fields, including molecular developmental biology, cancer research, endocrinology, and urology. Androgen signalling is mediated by the nuclear androgen receptor, which has fundamental roles in masculinization during development. Various modes of androgen signalling, including 5α-dihydrotestosterone-induced regulation of mesenchymal cell proliferation, have been observed in masculinization. Such regulation is essential for regulating urogenital tissue development, including external genitalia development. Androgen-induced genes, such as MAFB, which belongs to the activator protein 1 (AP-1) superfamily of genes, have essential roles in male urethral formation, and disruption of its signalling can interfere with urethral formation, which often results in hypospadias. Another AP-1 superfamily gene, ATF3, could be responsible for some instances of hypospadias in humans. These androgen-dependent signals and downstream events are crucial for not only developmental processes but also processes of diseases such as hypospadias and prostate cancer.



中文翻译:

男性化的调节:雄激素信号促进外生殖器发育

男性化生物学对于理解与男性生殖道,外部生殖器以及前列腺癌的发生有关的胚胎发育过程至关重要。在许多领域,包括分子发育生物学,癌症研究,内分泌学和泌尿科,许多研究人员和临床医生都对男性化的分子机制感兴趣。雄激素信号传导由核雄激素受体介导,该受体在发育过程中的男性化过程中具有基本作用。在男性化过程中,已观察到多种雄激素信号传导方式,包括5α-二氢睾丸激素诱导的间充质细胞增殖调控。这种调节对于调节泌尿生殖器组织的发育至关重要,包括外生殖器的发育。雄激素诱导的基因,例如MAFB,属于基因激活蛋白1(AP-1)的超家族,在男性尿道形成中具有重要作用,其信号传导中断可干扰尿道形成,这通常会导致尿道下裂。另一个AP-1超家族基因ATF3可能与人类尿道下裂的某些情况有关。这些雄激素依赖性信号和下游事件不仅对于发育过程而且对于诸如尿道下裂和前列腺癌等疾病的过程都至关重要。

更新日期:2018-04-18
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