Characteristics and inhibition by flavonoids of 20alpha-hydroxysteroid dehydrogenase activity in mouse tissues.
Progesterone was stereoselectively reduced to a metabolite 20alpha-hydroxy-4-pregnen-3-one in the cytosolic fraction from the liver of male mice, indicating that the reduction of progesterone is catalyzed by 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD). The cytosolic 20alpha-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 20alpha-HSD activity, although NADPH was better than NADH for the enzyme activity. On the other hand, 20alpha-HSD activity in kidney cytosol required only NADPH as a cofactor. No significant sex-related difference of 20alpha-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 20alpha-HSD activity. Thus, the effects of 16 flavonoids on 20alpha-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 20alpha-HSD activity. We propose the possibility that these flavonoids augment progesterone signaling by inhibiting potently 20alpha-HSD activity in non-reproductive tissues.
Shimada
Hideaki
H
Faculty of Education, Kumamoto University, 2-40-1, Kurokami, Kumamoto 860-8555, Japan. hshimada@gpo.kumamoto-u.ac.jp
Miura
Kazumi
K
Imamura
Yorishige
Y
D043607:20-alpha-Hydroxysteroid Dehydrogenase / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology
D005419:Flavonoids; D043607:20-alpha-Hydroxysteroid Dehydrogenase