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.
Cabeza
Marisa
M
Department of Biological Systems, Metropolitan University-Xochimilco, Mexico D. F., Mexico. marisa@cueyatl.uam.mx
Quiroz
Alexandra
A
Bratoeff
Eugene
E
García
Genoveva
G
Ramírez
Elena
E
Flores
Eugenio
E
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists / Q000494:pharmacology*; D001711:Biotransformation; D013196:Dihydrotestosterone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018120:Finasteride / Q000494:pharmacology; D007700:Kinetics; D010407:Penicillium / Q000201:enzymology*; D011282:Pregnenediones / Q000494:pharmacology*; D013739:Testosterone / Q000378:metabolism
C473847:4-bromo-17alpha-(p-fluorobenzoyloxy)-4-pregnene-3,20-dione; D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D004791:Enzyme Inhibitors; D011282:Pregnenediones; D013196:Dihydrotestosterone; D013739:Testosterone; D018120:Finasteride