Sex steroid receptor regulation by genistein in the prepubertal rat uterus

We evaluated the mechanism of action by the phytoestrogen genistein in the prepubertal rat uterus, when administered pharmacologically or physiologically. Female rats were injected with genistein (500 microg/g body weight), estradiol benzoate (EB) (500 ng/g body weight) or vehicle, dimethylsulfoxide (DMSO), on days 16, 18, and 20 postnatal. In 21-day-old rats, both compounds increased circulating estradiol and decreased progesterone concentrations. Uterine estrogen receptor alpha (ER-alpha) and androgen receptor (AR) proteins were reduced, and progesterone receptors (PR) were increased, as measured by western blot analyses. Immunohistochemistry for ER-alpha was confirmatory. Reverse transcription-polymerase chain reaction (RT-PCR) analyses indicated a decrease in ER-alpha, but not in ER-beta, PR and AR mRNA levels following genistein treatment. In prepubertal rats exposed perinatally to 250 mg genistein per kg AIN-76A diet or 250 microg estradiol per kg diet, uterine ER-alpha, AR, and PR proteins were not altered significantly. We conclude that pharmacologic, but not physiologic concentrations of genistein can modulate sex steroid receptor expression in the rat uterus.