Genistein Selectively Inhibits Estrogen-Induced Cell Proliferation and Other Responses to Hormone Stimulation in the Prepubertal Rat Uterus

Abstract

Sex hormone replacement therapy helps improve quality of life in climacteric women. However, estrogen-induced cell proliferation in the uterus and mammary gland increases the risk for cancer in these organs. The lower incidence of mammary cancer in Asian women than in western women has been attributed to high intake of soy isoflavones, including genistein. Our previous work in the prepubertal rat uterus model showed that genistein (0.5 mg/kg body weight subcutaneously) caused an estradiol-like hypertrophy in myometrial and uterine luminal epithelial cells and an increase in RNA content in luminal epithelium; however, it did not induce cell proliferation, uterine eosinophilia, or endometrial edema. The present study investigated, in the same animal model, the effect of genistein administration (0.5 mg/kg body weight subcutaneously) before treatment with estradiol-17β (0.33 mg/kg body weight subcutaneously) on uterine responses that were not induced by genistein. Pretreatment with this phytoestrogen completely inhibited estradiol-induced mitoses in uterine luminal epithelium, endometrial stroma, and myometrium and partially inhibited estradiol-induced uterine eosinophilia and endometrial edema. These findings indicate that genistein protects against estrogen-induced cell proliferation in the uterus and suggest that future studies should investigate the possibility of using this agent to decrease the risk for uterine cancer after hormone replacement therapy in climacteric women.

Soy Intake Since the Prepubertal Age May Contribute to the Pathogenesis of Endometriosis in Adulthood

“…20 Furthermore, the histological analysis of the uterine epithelium showed that, while the epithelium of soyfree-fed animals were presenting mitosis figures, that of soyfed animals exhibited both mitosis and necrosis figures. The literature reports that genistein, a soy-derived flavonoid, acts both as a selective estrogen agonist and a selective estrogen antagonist in the uterus of prepubertal rats, 21,22 unlike daidzein, another soy-derived flavonoid that was rather found to potentiate estrogen-induced cell proliferation in rat uterus. 23 Treatment of prepubertal rats with genistein was found to induce a hypertrophy of uterine epithelial cells, but not cell proliferation.…”

Effect of Prenatal Exposure to Lead on Estrogen Action in the Prepubertal Rat Uterus

“…The interaction of lead with hormone action may be direct, via qualitative or quantitative changes in hormone receptors [15], or caused by changes in levels of other hormones that modify the action of sex steroids, such as glucocorticoids [16] and prolactin [17], hormones that increase under the effect of exposure to lead [18]. Further, in agreement with the existence of independent mechanisms of estrogen action in the uterus that are involved in the generation of separate groups of responses to hormone stimulation, and the report of differences in the regulation of estrogen action in each uterine cell-type [16, 19–23], it was reported that exposure to lead dissociates responses to estrogen in the uterus: it selectively enhances some of these responses, inhibits others while a third group remains unaffected [12–14]. …”

Antiherpes evaluation of soybean isoflavonoids

“…Consequently, they can interact with estrogen receptors and mediate estrogenic responses, exerting estrogenic or antiestrogenic activity [1]. These effects have been extensively explored for hormone replacement therapy, as well as for anticarcinogenic effects [2][3][4]. Among the soy bioactive compounds, isoflavones are the most investigated group, especially genistein, daidzein, and glycitein.…”