title: Dietary genistein exerts estrogenic effects upon the uterus, mammary gland and the hypothalamic/pituitary axis in rats.
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 microg/g and 17, beta-estradiol at 1.0 microg/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 microg/g) increased uterine wet and dry weights (P < 0.05). Mammary gland regression following ovariectomy was significantly inhibited by dietary genistein at 750 microg/g (P < 0.05). Plasma prolactin was significantly greater in ovariectomized rats fed genistein (750 microg/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 microg/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 microg/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 microg/g was 2.2 micromol/L and free genistein was 0.4 micromol/L. Administration of dietary genistein at 750 microg/g can exert estrogenic effects in the uterus, mammary gland and hypothalamic/pituitary axis. Dietary genistein (750 microg/g) did not antagonize the action of estradiol in estradiol-supplemented ovariectomized rats or in intact rats.
authors.affiliation: Department of Food Science and Human Nutrition, Michigan State University, E. Lansing 48824, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Santell
authors.forename: Y C
authors.initials: YC
authors.lastname: Chang
authors.forename: M G
authors.initials: MG
authors.lastname: Nair
authors.forename: W G
authors.initials: WG
authors.lastname: Helferich
mesh_terms: D000284:Administration, Oral; D000821:Animal Feed; D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D019833:Genistein; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology; D007529:Isoflavones / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000254:growth & development; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011388:Prolactin / Q000097:blood; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000254:growth & development
chemical_list: D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D016760:Proto-Oncogene Proteins c-fos; D011960:Receptors, Estrogen; D004958:Estradiol; D011388:Prolactin; D019833:Genistein