A kinetic analysis of the inhibition of human prostatic 5 alpha-reductase by 4-hydroxyandrostenedione and related steroids.
The inhibition of human prostatic 5 alpha-reductase by androstenedione (A), 4-hydroxyandrostenedione (4-OH-A), and 4-methoxyandrostenedione (4-MeO-A) was studied. All three steroids inhibited 5 alpha-reductase in a concentration-dependent manner. The inhibition was competitive with respect to testosterone and non-competitive with respect to NADPH, indicating that these compounds inhibit 5 alpha-reductase by acting as alternative substrates. Ki values obtained were in the range 0.21-0.3 microM (A), 1.01-2.04 microM (4-OH-A), and 10.2-28.3 microM (4-MeO-A). Thus the two derivatives of androstenedione are poor inhibitors of 5 alpha-reductase and appear to have limited clinical potential.
Houston
B
B
University Department of Surgery, Western General Hospital, Edinburgh, Scotland.
Habib
F K
FK
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008297:Male; D011467:Prostate / Q000201:enzymology
D058891:5-alpha Reductase Inhibitors; C060445:4-methoxyandrostenedione; D000735:Androstenedione; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C014594:formestane