5α-Reduction of Epitestosterone Is Catalyzed by Human SRD5A1 and SRD5A2 and Increases Androgen Receptor Transactivation

This study investigates the metabolism of epitestosterone, a stereoisomer of testosterone, and its role in androgen receptor signalling. Researchers found that epitestosterone is metabolized to 5α-dihydroepitestosterone by human steroid 5α-reductase isoforms SRD5A1 and SRD5A2. Through reporter assays, it was demonstrated that epitestosterone acts as a partial agonist of the androgen receptor, and its 5α-reduction enhances its androgenic activity. Additionally, 5α-reduction diminishes epitestosterone's ability to antagonize 5α-dihydrotestosterone-induced receptor transactivation. The study concludes that steroid 5α-reductases play a role in modulating the effect of epitestosterone on androgen receptor signalling.