Phytoestrogens inhibit human 17 beta-hydroxysteroid dehydrogenase type 5

The 17 beta -hydroxysteroid dehydrogenase type 5 (17 beta -HSD 5) is involv ed in estrogen and androgen metabolism. In our study we tested the influenc e of environmental hormones, such as phytoestrogens (flavonoids, coumarins, coumestans), on reductive and oxidative 17 beta -HSD activity of the human 17 beta -hydroxysteroid dehydrogenase type 5 (17 beta -HSD 5). These dieta ry substances were shown to be potent inhibitors of aromatase, different 17 beta -HSDs and seem to play an important rule in delay of development of h ormone dependent cancers. Our studies show that reductive and oxidative act ivity of the enzyme are inhibited by many dietary compounds, especially zea ralenone. coumestrol, quercetin and biochanin A. Among the group of flavone s inhibitor potency is growing with increasing number of hydroxylations. We suggest that these substances are bound to the hydrophilic cofactor-bindin g pocket of the enzyme. An interesting inhibition pattern is observed for 1 8 beta -glycyrrhetinic acid, which has no influence on the oxidative but on ly on the reductive reaction. This indicates that this substrate binds to p H- and cofactor-depending sites at the active center of the enzyme. (C) 200 1 Elsevier Science Ireland Ltd. All rights reserved.