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

LIFE SCIENCES

卷:78

Article

Shimada, H ; Miura, K ; Imamura, Y

关键词: 20 alpha-hydroxysteroid dehydrogenase;    progesterone;    mouse tissues;    cofactor requirement;    flavonoids;    inhibitory potency;   

DOI  :  10.1016/j.lfs.2005.11.022

来源: Elsevier

【 摘 要 】

Progesterone was stereoselectively reduced to a metabolite 20 alpha-hydroxy-4-pregnen-3-one in the cytosolic fraction from the liver of male mice, indicating that the reduction of progesterone is catalyzed by 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD). The cytosolic 20 alpha-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 20 alpha-HSD activity, although NADPH was better than NADH for the enzyme activity. On the other hand, 20 alpha-HSD activity in kidney cytosol required only NADPH as a cofactor. No significant sex-related difference of 20 alpha-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 20 alpha-HSD activity. Thus, the effects of 16 flavonoids on 20 alpha-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 20 alpha-HSD activity. We propose the possibility that these flavonoids augment progesterone signaling by inhibiting potently 20 alpha-HSD activity in non-reproductive tissues. (c) 2005 Elsevier Inc. All rights reserved.

【 授权许可】

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