17α-Estradiol and Genistein Inhibit High Fat Diet Induced Prostate Gene Expression and Prostate Growth in the Rat

Abstract

High dietary fat and low phytoestrogen intake are associated with prostate cancer development and progression. Our previous study showed that exposure to a high fat diet significantly increased prostate 5α-reductase-2 mRNA and prostate growth in the rat. In the current experiments we determined the effects of genistein and 17α-estradiol on the modulation of dietary fat induced prostate 5α-reductase-2 and insulin-like growth factor-1 gene expression, and prostate growth. At weaning male ACI/Seg rats (Harlan® Sprague-Dawley®) were fed a low or a high fat diet, with or without genistein or 17α-estradiol for 2, 4 or 10 weeks. The prostate was dissected and weighed. We determined the levels of prostate 5α-reductase-2 mRNA, insulin-like growth factor-1 mRNA, dihydrotestosterone, and plasma insulin-like growth factor-1, dihydrotestosterone and testosterone. Two-week exposure to a high fat diet significantly increased prostate insulin-like growth factor-1 mRNA without significant changes in plasma insulin-like growth factor-1, which was blocked by genistein and 17α-estradiol. Genistein but not 17α-estradiol also inhibited prostate 5α-reductase-2 mRNA and intraprostatic dihydrotestosterone induced by the high fat diet at 2 weeks. Genistein and 17α-estradiol completely blocked high fat diet induced prostate growth at 10 weeks of dietary treatment. However, neither genistein nor 17α-estradiol had any significant effect when co-administered with the low fat diet. Results indicate that genistein and 17α-estradiol can inhibit dietary fat induced changes in prostate 5α-reductase-2 and insulin-like growth factor-1 gene expression, and prostate growth in the rat. This may be beneficial to prevent dietary fat associated prostate diseases such as prostate cancer.