Biosynthesis of Dihydrotestosterone by a Pathway That Does Not Require Testosterone as an Intermediate in the SZ95 Sebaceous Gland Cell Line

The study demonstrated that dihydrotestosterone (DHT) can be synthesized directly from dehydroepiandrosterone (DHEA) in SZ95 sebaceous gland cells, bypassing testosterone as an intermediate. This challenges the traditional view that DHT is produced from testosterone via 5α-reductase. The researchers used [¹4C]DHEA and inhibitors to trace the DHT biosynthesis pathway, finding that DHEA was rapidly converted to 4-androstenedione (4-dione) and then to 5α-androstane-3,17-dione (5α-dione), without forming testosterone. The application of finasteride, a 5α-reductase inhibitor, significantly reduced the levels of 5α-dione and DHT, indicating that 5α-dione is a precursor to DHT. This suggests an alternative DHT biosynthesis pathway: DHEA → 4-dione → 5α-dione → DHT, which could inform the development of targeted treatments for androgen-sensitive skin conditions.