Inhibitory effects of isoflavonoids on rat prostate testosterone 5α-reductase.

Testosterone 5α-reductase inhibitors represent important therapeutic drugs for use against androgen-dependent diseases such as benign prostatic hyperplasia, male pattern baldness, and acne. We have searched for inhibitors of rat prostate testosterone 5α-reductase in the cultured broths of many kinds of soil bacteria, and have found that cultured soybean-casein digest broths of certain bacterial strains have a potent inhibitory effect on the enzyme. We tested 10 selected isoflavonoids, including isoflavones and O-methylated isoflavones, for inhibitory effects on rat prostate testosterone 5α-reductase to determine the important structural elements for inhibition of the enzyme. Genistein, biochanin A, equol, and 3',4',7-trihydroxyisoflavone showed considerably higher inhibitory effects whereas daidzein, formononetin, glycitein, prunetin, ipriflavone, and 4',7-dimethoxyisoflavone showed lower inhibitory effects. The IC(50) values of genistein, biochanin A, equol, 3',4',7-trihydroxyisoflavone, and riboflavin, a positive control, for rat prostate testosterone 5α-reductase were 710 μm, 140 μm, 370 μm, 690 μm, and 17 μm, respectively. Daidzein, genistein, biochanin A, formononetin, and equol are already known to be testosterone 5α-reductase inhibitors, but this is the first characterization of 3',4',7-trihydroxyisoflavone as an inhibitor of the enzyme.