Diets high in selenium and isoflavones decrease androgen-regulated gene expression in healthy rat dorsolateral prostate

Reprod Biol Endocrinol. 2008 Nov 24:6:57. doi: 10.1186/1477-7827-6-57.

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

Conclusion: These results suggest that combined intake of high selenium and high isoflavones may achieve a greater chemopreventive effect than either compound supplemented individually.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Androgens / pharmacology*
  • Animal Feed / analysis
  • Animals
  • Diet* / veterinary
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects*
  • Isoflavones / administration & dosage
  • Isoflavones / analysis
  • Isoflavones / pharmacology*
  • Male
  • Osmolar Concentration
  • Prostate / drug effects*
  • Prostate / metabolism
  • Rats
  • Receptors, Androgen / physiology
  • Selenium / administration & dosage
  • Selenium / analysis
  • Selenium / pharmacology*

Substances

  • Androgens
  • Isoflavones
  • Receptors, Androgen
  • Selenium