Journal of Urology, 2011, 186(4):1489-96.

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

Liqun Cai, et al

Department of Medicine/Endocrinology, Weill Cornell Medical College, New York, New York 10065, USA; and Third Xiangya Hospital of Central South University (JC, YSZ), Changsha, People’s Republic of China

Purpose: 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.

MATERIALS AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

美国《泌尿学杂志》，2011年10月

在大鼠中17α-雌二醇和金雀异黄素抑制高脂饮食诱导的前列腺癌基因表达与前列腺生长

蔡立群等

美国纽约威尔康奈尔医学院医学/内分泌学系和中国长沙中南大学第三湘雅医院

目的︰高脂肪饮食和低植物激素摄入与前列腺癌的发生和发展有关。我们以前的研究显示，接触高脂肪饮食会明显增加大鼠前列腺 5 α-还原酶-2的 mRNA 和前列腺生长。在现在的实验中我们确定了染料木黄酮和17α- 雌二醇对膳食脂肪诱导的前列腺 5α-还原酶-2 和胰岛素样生长因子-1 基因表达和前列腺增长的影响。

材料和方法︰ 在断奶雄性 ACI/Seg大鼠 （Harlan® Sprague-Dawley®）被喂食低或高脂肪含量的饮食，含有/没有金雀异黄素或 17α-雌二醇 2、 4 或 10 周。前列腺被解剖，体重。我们确定了前列腺 5α-还原酶-2 mRNA、 胰岛素样生长因子-1 mRNA、 双氢睾酮和血浆胰岛素样生长因子-1，双氢睾酮和睾丸激素的水平。

结果︰ 两个星期接触高脂肪饮食明显提高了前列腺胰岛素样生长因子-1 mRNA 而血浆胰岛素样生长因子-1由于染料木素和17α-雌二醇的抑制没有明显变化。金雀异黄素而不是 17α- 雌二醇也抑制了前列腺 5α-还原酶-2 mRNA 并且前列腺双氢睾酮在接触了 2 周的高脂饮食后被诱导。染料木素和雌二醇 17α 完全阻塞在 10 周的膳食治疗高脂饮食诱导前列腺增长。然而，当与低脂肪饮食共同给药时，染料木黄酮和雌二醇 17α 都没有任何明显的影响。