Effects of Chronic Genistein Treatment in Mammary Gland, Uterus, and Vagina

BACKGROUND: The isoflavone genistein (GEN) is found in soy (Glycine max) and red clover (Trifolium pratense), The estrogenic activity of GEN is known, mid it is widely advertised as a phytoestrogen useful in alleviating climacteric complaints and other postmenopausal disorders. Knowledge of effects of long-term administration of GEN in laboratory animals is scarce, and effects in the uterus mid mammary gland after long-term administration have not been studied, The uterus and mammary gland are known to be negatively influenced by estrogens used in hormone therapy. OBJECTIVES: We administered two doses of GEN [mean daily uptake 5.4 (low) or 54 mg/kg (high) body weight (bw)] orally over a period of 3 months to ovariectomized (ovx) rats and compared the effects with a treatment with two doses of 17 beta-estradiol [E-2; 0.17 (low) or 0.7 mg/kg bw (high)]. Mammary glands, vaginae, and uteri were investigated morphologically and immunohistochemically. We quantified the expression of proliferating cell nuclear antigen (PCNA) and progesterone receptor (PR) in the mammary gland. RESULTS: In rats treated with either of the E-2 doses or the high GEN dose, we found increased uterine weight, and histologic analysis showed estrogen-induced features in the uteri, In vaginae, either E-2 dose or GEN high induced hyperplastic epithelium compared with the atrophic controls. In the mammary gland, E-2 (either dose) or GEN increased proliferation and PR expression. Serum levels of luteinizing hormone were decreased by E-2 (both doses) but not by GEN. CONCLUSIONS: In summary, E-2 and GEN share many effects in the studied organs, particularly in the vagina, uterus, and mammary gland but not in the hypothalamo/pituitary unit.