Figure 2.

T to DHT ratios in the prostate in various clinical states. Left, T to DHT ratios reported from independent studies. Benign prostate and untreated localized prostate cancer have concentrations of T ≪ DHT, with a ratio of approximately 1:10. In contrast, CRPC has concentrations of T > DHT, with an approximate ratio of 3:1. Pharmacological inhibition of SRD5A2 similarly increases the T to DHT ratio in benign prostate. Right, A model that explains these results in the context of the 5α-dione pathway in CRPC. In benign prostate, SRD5A2 robustly converts T to DHT. In CRPC, SRD5A1 robustly converts AD to 5α-dione. Although minor flux exists from AD to T, T is inefficiently converted to DHT by SRD5A1 and accumulates to concentrations above DHT. 5α-Dione concentrations have not been directly measured in CRPC and may also be determined in part by flux from 5α-dione to androsterone (not shown). Orange bars indicate the relative levels of the designated androgen.