Effect of a novel steroid (PM-9) on the inhibition of 5alpha-reductase present in Penicillium crustosum broths.

The conversion of testosterone (T) to 5alpha-dihydrotestosterone (DHT) has been demonstrated in Penicillium crustosum broth obtained from fermented pistachios, lemons and corn tortillas. Furthermore, the presence of 5alpha-reductase enzyme, which is responsible for this conversion, has been established by electrophoretical techniques in these cultures.5alpha-Reductase enzyme is also present in animal and human androgen-dependent tissues as well as in prostate and seminal vesicles. The increase of the conversion of T to DHT in prostate gland, has been related to some illnesses such as benign prostate hyperplasia and prostate cancer. Furthermore, treatment with 5alpha-reductase inhibitors such as finasteride reduces the prostate growth. These data have stimulated research for the synthesis of new molecules with antiandrogenic activity, whose biological effect needs to be demonstrated. The purpose of this study is to determine the inhibition pattern of 5alpha-reductase in P. crustosum by finasteride and the new steroidal compound PM-9. K(m) and V(max) values for T, were determined in the broths by Lineweaver-Burk plots using different testosterone concentrations. The inhibition pattern of finasteride and PM-9 was also determined by Lineweaver-Burk using different concentrations of T and inhibitors. Results show that finasteride and PM-9 inhibit 5alpha-reductase present in the broth in a competitive manner.

5 alpha-reductase inhibition by a new synthetic steroid (PM-9) in cultures of Penicillium crustosum.

The conversion of testosterone (T) to 5 alpha-dihydrotestosterone (DHT), plus the presence of 5 alpha-reductase enzyme, which is responsible for this reduction, had been demonstrated in P. crustosum broth. This enzyme is also present in androgen-dependent animal and human tissues such as prostate and seminal vesicles. The increase in the conversion of T to DHT has been implicated in androgen-dependent diseases such as benign prostate hyperplasia and prostate cancer. The use of 5 alpha-reductase inhibitors could mitigate these illnesses by inhibiting the DHT-receptor complex formation. The purpose of this study is to determine the inhibition pattern of 5 alpha-reductase by finasteride and PM-9 in P. crustosum broth. Km and Vmax values were determined in the broth by Lineweaver-Burk plots using different testosterone concentrations. The Km value was 0.22 microM and Vmax 0.833 pmol of DHT/mg of mycelium/day. The inhibition pattern of finasteride and PM-9 was also determined by Lineweaver-Burk plot, using different concentrations of T and inhibitors. The results of this study show that both finasteride and PM-9 inhibit 5 alpha-reductase in a competitive manner.