title: Human 17beta-hydroxysteroid dehydrogenase type 5 is inhibited by dietary flavonoids.
abstract: Phytoestrogens contained in a vegetarian diet are supposed to have beneficial effects on the development and progression of a variety of endocrine-related cancers. We have tested the effect of a variety of dietary phytoestrogens, especially flavonoids, on the activity of human 17beta-hydroxysteroid dehydrogenase type 5 (17beta-HSD 5), a key enzyme in the metabolism of estrogens and androgens. Our studies show that reductive and oxidative activity of the enzyme are inhibited by many compounds, especially zearalenone, coumestrol, quercetin and biochanin A. Among flavones, inhibitor potency is enhanced with increased degree of hydroxylation. The most effective inhibitors seem to bind to the hydrophilic cofactor binding pocket of the enzyme.
authors.affiliation: GSF-National Research Center for Environment and Health, Institute for Experimental Genetics, Genome Analysis Center, Neuherberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Krazeisen
authors.forename: R
authors.initials: R
authors.lastname: Breitling
authors.forename: G
authors.initials: G
authors.lastname: Möller
authors.forename: J
authors.initials: J
authors.lastname: Adamski
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D015096:3-Hydroxysteroid Dehydrogenases; D000074425:Aldo-Keto Reductase Family 1 Member C3; D015113:Androstane-3,17-diol / Q000378:metabolism; D000735:Androstenedione / Q000378:metabolism; D000738:Androsterone / Q000096:biosynthesis; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D004032:Diet; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006900:Hydroxylation; D006911:Hydroxyprostaglandin Dehydrogenases; D007529:Isoflavones; D009376:Neoplasms, Hormone-Dependent / Q000517:prevention & control; D010084:Oxidation-Reduction; D048789:Phytoestrogens; D028321:Plant Preparations; D010945:Plants, Edible / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000494:pharmacology; D013739:Testosterone / Q000096:biosynthesis
chemical_list: D016588:Anticarcinogenic Agents; D004791:Enzyme Inhibitors; D004968:Estrogens, Non-Steroidal; D005419:Flavonoids; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D011993:Recombinant Fusion Proteins; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D015113:Androstane-3,17-diol; D013739:Testosterone; D000735:Androstenedione; D000738:Androsterone; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D006911:Hydroxyprostaglandin Dehydrogenases; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3