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 physiologica lly. Female rats were injected with genistein (500 mug/g body weight), estr adiol benzoate (EB) (500 ng/g body weight) or vehicle. dimethylsulfoxide (D MSO), 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) prote ins were reduced, and progesterone receptors (PR) were increased, as measur ed by western blot analyses. Immunohistochemistry for ER-alpha was confirma tory. Reverse transcription polymerase chain reaction IRT PCR) analyses ind icated a decrease in ER-alpha. but not in ER-beta. PR and AR mRNA levels fo llowing genistein treatment. In prepubertal rats exposed perinatally to 250 mg genistein per kg AIN-76A diet or 250 mug 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 mod ulate sex steroid receptor expression in the rat uterus. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.