Dietary genistein down-regulates androgen and estrogen receptor expression in the rat prostate
Dietary genistein down-regulates androgen and estrogen receptor expression in the rat prostate
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DOI：
10.1016/s0303-7207(01)00663-3
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发表时间：
2002-01-15
影响因子：
4.1
通讯作者：
Lamartiniere, CA
中科院分区：
文献类型：
--
作者：
Fritz, WA;Wang, J;Lamartiniere, CA
美国和欧洲有临床表现的前列腺癌的发病率高于亚洲国家。这些人群生活方式的主要差异之一是饮食，亚洲人消费更多的大豆。大豆和染料木黄酮（大豆中发现的主要异黄酮）可抑制动物模型中前列腺肿瘤的发展。本研究的目的是研究膳食染料木黄酮对背外侧前列腺中性类固醇受体表达、循环雄激素的影响，以及对雄性大鼠生殖道的潜在毒性。雄性Sprague-Dawley大鼠从受孕到产后70天喂食25和250 mg金雀异黄素/kg饮食，或从产后56到70天喂食250和1000 mg金雀异黄素/kg饮食。从受孕开始，饮食中暴露于金雀异黄酮会导致背外侧前列腺中雄激素受体（AR）和雌激素受体（ER）-α和-β mRNA表达以剂量依赖性方式下调。此外，给成年大鼠喂食金雀异黄酮两周，可降低背外侧前列腺中 AR、ER-α 和 ER-β 的 mRNA 表达。与对照动物相比，饲喂 1000 mg 金雀异黄素/kg 饮食的动物 ER-α 蛋白水平显着降低。男性生殖道组织形态或重量没有显着改变。我们得出的结论是，饮食金雀异黄素下调大鼠前列腺中 AR 和 ER-α 和 β 的表达，其浓度与人类大豆饮食中发现的浓度相当。性类固醇受体表达下调可能是饮食含有高水平植物雌激素的人群中前列腺癌发病率较低的原因。 (C) 2002 Elsevier Science Ireland Ltd. 保留所有权利。
The incidence of clinically manifested prostate cancer is higher in the United States and Europe than in Asian countries. One of the major differences in lifestyle between these populations is the diet, with Asians consuming a greater amount of soy. Soy and genistein, the predominant isoflavone found in soy, inhibit prostate tumor development in animal models. The purpose of this study was to investigate the effect of dietary genistein on sex steroid receptor expression in the dorsolateral prostate, on circulating androgens, and the potential for toxicity in the male rat reproductive tract. Male Sprague-Dawley rats were fed 25 and 250 mg genistein/kg diet from conception until day 70 postpartum, or 250 and 1000 mg genistein/kg diet from day 56 to 70 postpartum. Exposure to genistein in the diet, starting at conception, resulted in down-regulated androgen receptor (AR), and estrogen receptors (ER)-alpha and -beta mRNA expression in the dorsolateral prostate in a dose-dependent manner. Also, genistein fed to adult rats for 2 weeks reduced mRNA expression of AR, ER-alpha and ER-beta in the dorsolateral prostate. ER-alpha protein levels were significantly reduced in animals fed 1000 mg genistein/kg diet compared to control animals. There were no significant alterations to male reproductive tract histomorphology or weights. We conclude that dietary genistein down-regulated expression of the AR and ER-alpha and -beta in the rat prostate at concentrations comparable to those found in humans on a soy diet. Down-regulated sex steroid receptor expression may be responsible for the lower incidence of prostate cancer in populations on a diet containing high levels of phytoestrogens. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.