Regulation of masculinization: Androgen signalling for external genitalia development

Shoko Matsushita, Kentaro Suzuki, Aki Murashima, Daiki Kajioka, Alvin Resultay Acebedo, Shinichi Miyagawa, Ryuma Haraguchi, Yukiko Ogino, Gen Yamada

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)358-368
Number of pages11
JournalNature Reviews Urology
Volume15
Issue number6
DOIs
Publication statusPublished - 1 Jun 2018

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Matsushita, S., Suzuki, K., Murashima, A., Kajioka, D., Acebedo, A. R., Miyagawa, S., Haraguchi, R., Ogino, Y., & Yamada, G. (2018). Regulation of masculinization: Androgen signalling for external genitalia development. Nature Reviews Urology, 15(6), 358-368. https://doi.org/10.1038/s41585-018-0008-y