title: Influence of testosterone on phase II metabolism and availability of soy isoflavones in male Wistar rats.
abstract: Genistein and daidzein are the main isoflavones in soy. Their potential beneficial or adverse effects in males like the prevention of prostate cancer or the impact on reproductive functions are controversially discussed. Major determinants of their bioactivity are the absorption and biotransformation of isoflavones. In this study, we focused on the influence of testosterone on plasma availability and phase II metabolism of isoflavones. Male Wistar rats, receiving an isoflavones rich diet, were randomized into three groups: Two groups were orchiectomized (ORX) at postnatal day (PND) 80 and treated for 11 days with testosterone propionate (TP) (ORX TP group) or a vehicle (ORX group) after a 7 days lasting hormonal decline. The third group served as control and remained intact. Rats were sacrificed at PND 98. ORX rats had reduced isoflavones plasma levels. Differently regulated mRNA expressions of transporters relevant for transport of phase II metabolites in liver and kidney may be responsible for this reduction, more precisely Slc10a1 and Slc21a1 in kidney as well as Slc22a8 in liver. While main phase II metabolites in intact rats were disulfates and sulfoglucuronides, the amount of sulfate conjugates was significantly diminished by ORX. In accordance with that, mRNA expression of different sulfotransferases was reduced in liver by ORX. The observed effects could be almost restored by TP treatment. In conclusion, testosterone, and likely further androgens, has a huge impact on phase II metabolism and availability of isoflavones by influencing the expression of different sulfotransferases and transporters.
authors.affiliation: Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Haid-und-Neu-Straße 9, 76131, Karlsruhe, Germany.
authors.forename: Sebastian T
authors.initials: ST
authors.lastname: Soukup
authors.affiliation: Department of Molecular and Cellular Sports Medicine, German Sport University Cologne, Cologne, Germany.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Müller
authors.affiliation: Department of Molecular and Cellular Sports Medicine, German Sport University Cologne, Cologne, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Kurrat
authors.affiliation: Department of Molecular and Cellular Sports Medicine, German Sport University Cologne, Cologne, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Diel
authors.affiliation: Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Haid-und-Neu-Straße 9, 76131, Karlsruhe, Germany. sabine.kulling@mri.bund.de.
authors.forename: Sabine E
authors.initials: SE
authors.lastname: Kulling
mesh_terms: D000818:Animals; D007529:Isoflavones / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009919:Orchiectomy; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013025:Glycine max / Q000737:chemistry; D027981:Symporters / Q000235:genetics; D043343:Testosterone Propionate / Q000494:pharmacology*
chemical_list: D007529:Isoflavones; D026901:Membrane Transport Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D029362:Organic Anion Transporters, Sodium-Independent; D012333:RNA, Messenger; C421102:Slco1a1 protein, rat; D027981:Symporters; C114338:organic anion transport protein 3; C071908:sodium-bile acid cotransporter; C040641:genistin; C004742:daidzein; D043343:Testosterone Propionate
keywords: Genistein; Phase II metabolism; Soy isoflavones; Sulfates; Sulfoglucuronides; Testosterone