Regulation of masculinization: androgen signalling for external genitalia development
Regulation of masculinization: androgen signalling for external genitalia development
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DOI：
10.1038/s41585-018-0008-y
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发表时间：
2018-06
影响因子：
15.3
通讯作者：
S. Matsushita;Kentarou Suzuki;A. Murashima;Daiki Kajioka;A. R. Acebedo;S. Miyagawa;Ryuma Haraguchi;Y. Ogino;G. Yamada
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文献类型：
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作者：
S. Matsushita;Kentarou Suzuki;A. Murashima;Daiki Kajioka;A. R. Acebedo;S. Miyagawa;Ryuma Haraguchi;Y. Ogino;G. Yamada
男性化的生物学对于理解涉及男性生殖道、外生殖器发育以及前列腺癌肿瘤发生的胚胎发育过程至关重要。男性化的分子机制是许多研究人员和临床医生感兴趣的不同领域，包括分子发育生物学，癌症研究，内分泌学和泌尿学。雄激素信号传导由核雄激素受体介导，其在发育期间的雄性化中具有基本作用。在雄性化过程中观察到各种雄激素信号传导模式，包括5α-二氢睾酮诱导的间充质细胞增殖调节。这种调节对于调节泌尿生殖器组织发育，包括外生殖器发育是必不可少的。雄激素诱导的基因，如MAFB，它属于激活蛋白1（AP-1）基因超家族，在男性尿道形成中具有重要作用，其信号传导的中断可干扰尿道形成，这通常导致尿道下裂。另一个AP-1超家族基因，ATF 3，可能是导致人类尿道下裂的原因。这些雄激素依赖性信号和下游事件不仅对发育过程至关重要，而且对尿道下裂和前列腺癌等疾病的过程也至关重要。
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 asMAFB, 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.