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Phytoestrogens inhibit human 17beta-hydroxysteroid dehydrogenase type 5
A Krazeisen1, R Breitling, G Möller
1GSF National Research Center for Environment and Health, Institute for Experimental Genetics, Genome Analysis Center, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany.
Molecular and Cellular Endocrinology
|February 13, 2001
Summary
Environmental hormones like phytoestrogens can inhibit 17beta-hydroxysteroid dehydrogenase type 5 (17beta-HSD 5) enzyme activity. This finding is crucial for understanding hormone-dependent cancers and developing potential therapeutic strategies.
Area of Science:
- Biochemistry
- Endocrinology
- Pharmacology
Background:
- 17beta-hydroxysteroid dehydrogenase type 5 (17beta-HSD 5) plays a key role in estrogen and androgen metabolism.
- Environmental hormones, including phytoestrogens, are known to influence various enzymatic pathways.
- These compounds have demonstrated inhibitory effects on aromatase and other 17beta-HSDs, suggesting a role in hormone-dependent cancer prevention.
Purpose of the Study:
- To investigate the impact of environmental hormones (phytoestrogens) on the reductive and oxidative activity of human 17beta-HSD 5.
- To identify specific dietary compounds that inhibit 17beta-HSD 5 activity.
- To elucidate the binding mechanisms of these inhibitors to the enzyme.
Main Methods:
- Enzyme assays were conducted to measure the reductive and oxidative activity of 17beta-HSD 5.
- A panel of dietary compounds, including flavonoids, coumarins, and coumestans, were tested for their inhibitory effects.
- Structure-activity relationships were analyzed for flavone inhibitors.
Main Results:
- Many dietary compounds, notably zearalenone, coumestrol, quercetin, and biochanin A, significantly inhibited both reductive and oxidative 17beta-HSD 5 activity.
- Inhibitor potency among flavones increased with a higher number of hydroxylations.
- 18beta-glycyrrhetinic acid selectively inhibited the reductive activity, suggesting distinct binding sites for oxidative and reductive reactions.
Conclusions:
- Phytoestrogens and other dietary compounds are potent inhibitors of 17beta-HSD 5.
- The findings suggest these compounds bind to the cofactor-binding pocket, with structural features influencing potency.
- Selective inhibition by compounds like 18beta-glycyrrhetinic acid highlights specific interactions within the enzyme's active site, offering insights for targeted drug design.