Figure 4.
The pattern of observed metabolic flux differs between samples from patients on a 5-ARI at time of surgery (n=3) versus patients who were treatment-naïve (n=9). A) [13C3]-5α-dione is the predominant metabolite arising from [13C3]-AD in all patients at 24 hours of incubation. However, formation of [13C3]-5α-dione is notably reduced in patients confirmed to be on a 5-ARI at the time of surgery (denoted by red asterisks). B) DHTunl is the predominant metabolite arising from Tunl at 24 hours except in patients on a 5-ARI, in which case Tunl was rapidly converted to ADunl instead (red asterisks). C-D) Although no Tunl→DHTunl conversion was observed in any samples from patients on a 5-ARI, residual [13C3]-AD→[13C3]-5α-dione→[13C3]-DHT conversion remained. E) Only a modest increase in alternative metabolic flux of [13C3]-AD to [13C3]-T is observed despite pharmacologic inhibition of 5α-reduction and accumulation of [13C3]-AD, indicating that 17-keto reduction of AD is overall limited in prostatic tissue. Error bars represent the SEM.