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 alpha and beta (ER alpha and beta), with preferential affinity for ER beta. 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 ER alpha and ER beta 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 F(1) and F(2) 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 ER alpha and ER beta 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 F(1) generation, but they were not accompanied by organ weight changes. Body weight in the continuously dosed 500 ppm F(1) 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 ER beta 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 F(1) rats, but not in F(2) rats. Given the growing body of knowledge on the significance of ER beta 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.
Dalu
Abraham
A
Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
Blaydes
Betty S
BS
Bryant
Corey W
CW
Latendresse
John R
JR
Weis
Constance C
CC
Barry Delclos
K
K
D000818:Animals; D004032:Diet; D013196:Dihydrotestosterone / Q000097:blood; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011467:Prostate / Q000033:anatomy & histology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism*; D013739:Testosterone / Q000097:blood
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen; D013196:Dihydrotestosterone; D013739:Testosterone; D019833:Genistein