Dietary Genistein Exerts Estrogenic Effects upon the Uterus, Mammary Gland and the Hypothalamic/Pituitary Axis in Rats

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Abstract
These studies were undertaken to assess the estrogenic and antiestrogenic effects of dietary genistein. To determine estrogenic effects, genistein was mixed into a modified AIN-76 or AIN-93G semipurified diet at 0 (negative control), 150, 375 or 750 μg/g and 17, β-estradiol at 1.0 μg/g and fed to ovariectomized 70-d-old Sprague-Dawley rats. Estrogenic potency was determined by analyzing uterine weight, mammary gland development, plasma prolactin and expression of uterine c-fos. Dietary genistein (375 and 750 μg/g) increased uterine wet and dry weights (P < 0.05). Mammary gland regression following ovariectomy was significantly inhibited by dietary genistein at 750 μg/g (P < 0.05). Plasma prolactin was significantly greater in ovariectomized rats fed genistein (750 μg/g) compared with comparable rats not receiving genistein. The relative binding affinity of genistein to the estrogen receptor (ER) was ∼0.01 that of estradiol. Genistein (750 μg/g) induced the uterine expression of c-fos. To evaluate potential antiestrogenic effects, genistein and estradiol were mixed into the modified AIN diets at the doses noted above and fed to ovariectomized rats. Dietary genistein (375 or 750 μg/g) did not inhibit the effects of estradiol on uterine weight, mammary gland development or plasma prolactin. Serum concentration of total genistein (conjugated plus free) in rats fed 750 μg/g was 2.2 μmol/L and free genistein was 0.4 μmol/L. Administration of dietary genistein at 750 μg/g can exert estrogenic effects in the uterus, mammary gland and hypothalamic/pituitary axis. Dietary genistein (750 μg/g) did not antagonize the action of estradiol in estradiol-supplemented ovariectomized rats or in intact rats.