Characteristics and inhibition by flavonoids of 20α-hydroxysteroid dehydrogenase activity in mouse tissues

Progesterone was stereoselectively reduced to a metabolite 20α-hydroxy-4-pregnen-3-one in the cytosolic fraction from the liver of male mice, indicating that the reduction of progesterone is catalyzed by 20α-hydroxysteroid dehydrogenase (20α-HSD). The cytosolic 20α-HSD activity was observed not only in the liver, but also in the kidney and lung. In liver cytosol, both NADPH and NADH were effective as cofactors for 20α-HSD activity, although NADPH was better than NADH for the enzyme activity. On the other hand, 20α-HSD activity in kidney cytosol required only NADPH as a cofactor. No significant sex-related difference of 20α-HSD activity was observed in liver and kidney cytosols. Flavonoids have been reported to inhibit the biosynthesis and metabolism of steroids. However, little is known about inhibitory effects of flavonoids on 20α-HSD activity. Thus, the effects of 16 flavonoids on 20α-HSD activity were examined, using liver cytosol of male mice. Among flavonoids tested, fisetin, apigenin, naringenin, luteolin, quercetin and kaempferol exhibited high inhibitory potencies for the 20α-HSD activity. We propose the possibility that these flavonoids augment progesterone signaling by inhibiting potently 20α-HSD activity in non-reproductive tissues.