title: Phytoestrogens inhibit human 17beta-hydroxysteroid dehydrogenase type 5.
abstract: The 17beta-hydroxysteroid dehydrogenase type 5 (17beta-HSD 5) is involved in estrogen and androgen metabolism. In our study we tested the influence of environmental hormones, such as phytoestrogens (flavonoids, coumarins, coumestans), on reductive and oxidative 17beta-HSD activity of the human 17beta-hydroxysteroid dehydrogenase type 5 (17beta-HSD 5). These dietary substances were shown to be potent inhibitors of aromatase, different 17beta-HSDs and seem to play an important role in delay of development of hormone dependent cancers. Our studies show that reductive and oxidative activity of the enzyme are inhibited by many dietary compounds, especially zearalenone, coumestrol, quercetin and biochanin A. Among the group of flavones inhibitor potency is growing with increasing number of hydroxylations. We suggest that these substances are bound to the hydrophilic cofactor-binding pocket of the enzyme. An interesting inhibition pattern is observed for 18beta-glycyrrhetinic acid, which has no influence on the oxidative but only on the reductive reaction. This indicates that this substrate binds to pH- and cofactor-depending sites at the active center of the enzyme.
authors.affiliation: GSF National Research Center for Environment and Health, Institute for Experimental Genetics, Genome Analysis Center, Ingolstädter Landstrasse 1, 85764, 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* / Q000737:chemistry / Q000235:genetics; D047072:Aromatase Inhibitors; D001665:Binding Sites; D001943:Breast Neoplasms / Q000517:prevention & control; D003375:Coumestrol / Q000494:pharmacology; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D019833:Genistein / Q000494:pharmacology; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006900:Hydroxylation; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007529:Isoflavones; D008297:Male; D008958:Models, Molecular; D010084:Oxidation-Reduction; D048789:Phytoestrogens; D028321:Plant Preparations; D011471:Prostatic Neoplasms / Q000517:prevention & control; D011794:Quercetin / Q000494:pharmacology; D011994:Recombinant Proteins; D013025:Glycine max; D013739:Testosterone / Q000378:metabolism; D015025:Zearalenone / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D004968:Estrogens, Non-Steroidal; D007527:Isoenzymes; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D011994:Recombinant Proteins; D013739:Testosterone; D015025:Zearalenone; D011794:Quercetin; D019833:Genistein; D015067:17-Hydroxysteroid Dehydrogenases; D006034:Glycyrrhetinic Acid; C004541:biochanin A; D003375:Coumestrol