Molecular Mechanisms of Androgen Action

This chapter describes the molecular mechanisms of androgen action. Androgens are pervasive in their effects on the development, maintenance, and regulation of male phenotype and reproductive physiology in adult males. In addition, androgens are implicated in a number of human pathologies. Testosterone (T), the dominant testicular androgen, diffuses passively into the cell and either binds directly to the androgen receptor (AR), undergoes enzymatic reduction to 5a-dihydrotestosterone (DHT), or undergoes aromatization to estrogens. Once T or DHT binds to the AR, the protein undergoes conformational changes, chaperone proteins such as heat shock proteins dissociate from the receptor, and the activated receptor can then bind DNA. Differentiation of external genitalia from the genital tubercle, urethral folds, labioscrotal folds, and urogenital sinus is mediated by DHT. The genital tubercle gives rise to the glans penis and corpus cavernosum whereas the urethral folds and labioscrotal swellings give rise to portions of the penis and scrotum. The mechanisms by which testicular androgens masculinize the nervous system vary from species to species and from site to site.