DIETARY GENISTEIN EXERTS ESTROGENIC EFFECTS UPON THE UTERUS, MAMMARY-GLAND AND THE HYPOTHALAMIC PITUITARY AXIS IN RATS/

These studies were undertaken to assess the estrogenic and antiestroge nic effects of dietary genistein. To determine estrogenic effects, gen istein was mixed into a modified AIN-76 or AIN-93G semipurified diet a t 0 (negative control), 150, 375 or 750 mu g/g and 17, beta-estradiol at 1.0 mu g/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 mu g/g) increased uterine wet and dry w eights (P < 0.05). Mammary gland regression following ovariectomy was significantly inhibited by dietary genistein at 750 mu g/g (P < 0.05). Plasma prolactin was significantly greater in ovariectomized rats fed genistein (750 mu g/g) compared with comparable rats not receiving ge nistein. The relative binding affinity of genistein to the estrogen re ceptor (ER) was similar to 0.01 that of estradiol. Genistein (750 mu g /g) induced the uterine expression of c-fos. To evaluate potential ant iestrogenic effects, genistein and estradiol were mixed into the modif ied AIN diets at the doses noted above and fed to ovariectomized rats. Dietary genistein (375 or 750 mu g/g) did not inhibit the effects of estradiol on uterine weight, mammary gland development or plasma prola ctin. Serum concentration of total genistein (conjugated plus free) in rats fed 750 mu g/g was 2.2 mu mol/L and free genistein was 0.4 mu mo l/L. Administration of dietary genistein at 750 mu g/g can exert estro genic effects in the uterus, mammary gland and hypothalamic/pituitary axis. Dietary genistein (750 mu g/g) did not antagonize the action of estradiol in estradiol-supplemented ovariectomized rats or in intact r ats.