Effect of Dietary Soy Isoflavone Aglycones on the Urinary 16α-to-2-Hydroxyestrone Ratio in C3H/HeJ Mice

Abstract

Estradiol is metabolized through two mutually exclusive pathways. 2-Hydroxyestrone (2-OHE₁) is antiestrogenic, while 16α-hydroxyestrone (16α-OHE₁) is a potent estrogen. It is suggested that a high urinary 16α-OHE₁-to-2-OHE₁ rato is a biomarker of increased mammary tumor risk. Mice were fed one of the test diets for 21 days. Indole-3-carbinol (2,500 mg/kg diet) increased the cytochrome P-450 content of hepatic microsomes and liver weight and reduced the urinary 16α-OHE₁-to-2-OHE₁ ratio in comparison with the respective value in the control mice. Fermented soy extract (100, 200, or 400 mg isoflavonoid/kg diet), genistein (200 mg/kg diet), and daidzein (200 mg/kg diet) each reduced the urinary 16α-OHE₁-to-2-OHE₁ ratio without increasing the cytochrome P-450 content of hepatic microsomes or liver weight. The combination of genistein and daidzein (100 mg and 100 mg/kg diet) did not have a synergistic effect on the reduction in urinary 16α-OHE₁-to-2-OHE₁ ratio. These data suggest that the soy isoflavonoid aglycones genistein and daidzein and indole-3-carbinol each exert a cancer-preventive effect by shifting metabolism away from the production of genotoxic metabolites toward the production of inactive metabolites.