Internal medicine

Androgen

Hypospadias

Dihydrotestosterone

Prostate cancer

Carcinogenesis

Androgen receptor

Nuclear receptor

Transcription factor

Biology

Gene

Cancer

Endocrinology

Prostate

Disorders of sex development

Cancer research

Genetics

Sexual differentiation

Hormone

Medicine

Nature Reviews Urology

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. The biology of masculinization is important for understanding embryonic developmental processes involved in the development of the male reproductive tract, genitalia and tumorigenesis of prostate cancer. In this Review, the authors describe our current understanding of the regulation of masculinization.

Regulation of masculinization: androgen signalling for external genitalia development