title: Diets high in selenium and isoflavones decrease androgen-regulated gene expression in healthy rat dorsolateral prostate.
abstract: BACKGROUND
  High dietary intake of selenium or soybean isoflavones reduces prostate cancer risk. These components each affect androgen-regulated gene expression. The objective of this work was to determine the combined effects of selenium and isoflavones on androgen-regulated gene expression in rat prostate.
  
  
  METHODS
  Male Noble rats were exposed from conception until 200 days of age to diets containing an adequate (0.33-0.45 mg/kg diet) or high (3.33-3.45 mg/kg) concentration of selenium as Se-methylselenocysteine and a low (10 mg/kg) or high (600 mg/kg) level of isoflavones in a 2 x 2 factorial design. Gene expression in the dorsolateral prostate was determined for the androgen receptor, for androgen-regulated genes, and for Akr1c9, whose product catalyzes the reduction of dihydrotestosterone to 5alpha-androstane-3alpha, 17beta-diol. Activity of hepatic glutathione peroxidise 1 and of prostatic 5alpha reductase were also assayed.
  
  
  RESULTS
  There were no differences due to diet in activity of liver glutathione peroxidase activity. Total activity of 5alpha reductase in prostate was significantly lower (p = 0.007) in rats fed high selenium/high isoflavones than in rats consuming adequate selenium/low isoflavones. High selenium intake reduced expression of the androgen receptor, Dhcr24 (24-dehydrocholesterol reductase), and Abcc4 (ATP-binding cassette sub-family C member 4). High isoflavone intake decreased expression of Facl3 (fatty acid CoA ligase 3), Gucy1a3 (guanylate cyclase alpha 3), and Akr1c9. For Abcc4 the combination of high selenium/high isoflavones had a greater inhibitory effect than either treatment alone. The effects of selenium on gene expression were always in the direction of chemoprevention
  
  
  CONCLUSIONS
  These results suggest that combined intake of high selenium and high isoflavones may achieve a greater chemopreventive effect than either compound supplemented individually.
authors.affiliation: Department of Nutrition, Dietetics and Food Science, Brigham Young University, Provo, UT 84602, USA. rj_legg@netzero.net
authors.forename: Russell L
authors.initials: RL
authors.lastname: Legg
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Tolman
authors.forename: Cameron T
authors.initials: CT
authors.lastname: Lovinger
authors.forename: Edwin D
authors.initials: ED
authors.lastname: Lephart
authors.forename: Kenneth D R
authors.initials: KD
authors.lastname: Setchell
authors.forename: Merrill J
authors.initials: MJ
authors.lastname: Christensen
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000821:Animal Feed / Q000032:analysis; D000818:Animals; D004032:Diet / Q000662:veterinary; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D007529:Isoflavones / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D009994:Osmolar Concentration; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011944:Receptors, Androgen / Q000502:physiology; D012643:Selenium / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*
chemical_list: D000728:Androgens; D007529:Isoflavones; D011944:Receptors, Androgen; D012643:Selenium