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Manuscript received April 1996. Initial reviews completed 6 June 1996. Revision accepted 25 October 1996.
Department of Food Science and Human Nutrition, * Department of Horticulture, Michigan State University, E. Lansing, MI 48824
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, 
-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.
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