Estrogen receptor expression in the prostate of rats treated with dietary genistein

Steroid hormones and their receptors play critical roles in the growth, development, and maintenance of the male reproductive tract. Genistein, a naturally occurring isoflavonoid primarily found in soybeans, interacts with estrogen receptors α and β (ERα and β), with preferential affinity for ERβ. This is one mechanism whereby genistein may affect growth and development and potentially alter susceptibility to carcinogenesis. Previous studies have indicated effects of soy and/or genistein in the male rodent reproductive tract under certain exposure conditions. The current study was undertaken to determine if modulation of the expression of ERα and ERβ by dietary genistein may contribute to those effects. Rats in a two-generation study were fed 0, 5, 100, or 500 ppm genistein prior to mating and through pregnancy and lactation. At weaning, male pups were selected in each of the F1 and F2 generations and half of the pups continued on the same diet as their dams (G/G, continuous exposure) while their litter mates were placed on control chow (G/C, gestational and lactational exposure) until sacrifice on PND 140. Male reproductive organ weights, serum levels of testosterone and dihydrotestosterone (DHT), and ERα and ERβ protein levels in the ventral and dorsolateral prostate were the endpoints measured. Prostate sections were also evaluated microscopically. Statistically significant elevations in testosterone and DHT were observed in PND 140 animals from the F1 generation, but they were not accompanied by organ weight changes. Body weight in the continuously dosed 500 ppm F1 PND 140 animals was depressed relative to control, but organ weights in animals of either generation showed few treatment-related effects. While estrogen receptor levels were quite variable, levels of ERβ in the dorsolateral prostate were significantly depressed in all dose groups in the G/C exposure and the high dose group of the G/G exposure in F1 rats, but not in F2 rats. Given the growing body of knowledge on the significance of ERβ in the prostate, the evidence for apparent down regulation of this receptor by genistein may have implications for reproductive toxicity and carcinogenesis that warrant further investigation.