Molecular Nutrition & Food Research, 2012, 56(3):399–409.

In utero and postnatal exposure to isoflavones results in a reduced responsivity of the mammary gland towards estradiol

Almut F Molzberger, Gunter Vollmer, Torsten Hertrampf, et al

Department of Molecular and Cellular Sports Medicine, German Sports University Cologne, Germany; et al

SCOPE:

Exposure scenarios during different stages of development of an organism are discussed to trigger adverse and beneficial effects of isoflavones (ISO). The aim of this study was to investigate how in utero and postnatal ISO exposure modulates the estrogen sensitivity of the mammary gland and to identify the underlying molecular mechanisms.

METHODS AND RESULTS:

Therefore, rats were exposed to either ISO-free (IDD), ISO-rich (IRD) or genistein-rich diet (GRD), up to young adulthood. Proliferative activity (PCNA expression) in the mammary gland at different ages and the estrogen sensitivity of the mammary gland to estradiol (E₂) or genistein (GEN) in adult ovariectomized animals was determined and compared with different treatments. Treatment with E₂ resulted in a significant lower proliferative and estrogenic response of the mammary gland in IRD and GRD compared with IDD. This correlates to a change in the gene expression pattern and a decrease in the ratio of estrogen receptor alpha (ERα) beta (ERβ).

CONCLUSIONS:

Our results provide evidence that in utero and postnatal exposure to a diet rich in ISO but also to GEN reduces the sensitivity of the mammary gland toward estrogens and support the hypothesis that in utero and postnatal ISO exposure reduces the risk to develop breast cancer.

德国《分子营养与食品研究》，2012年3月

在子宫内和出生后暴露于异黄酮导致乳腺组织对雌激素的响应降低

奥尔玛特 F 毛尔斯伯格，冈特尔 沃尔默，托斯顿 赫特兰普夫，等

德国科隆体育大学分子和细胞运动医学学院等

目标︰

对有机体不同阶段发展的曝光情况进行了探讨，触发了异黄酮 (ISO) 的不利和有利影响。本研究的目的是探讨在子宫内和产后 ISO 接触怎样调节乳腺组织对雌激素的敏感性，并确定其潜在的分子机制。

方法和结果︰

因此，大鼠接触 ISO–无(IDD)、 ISO-丰富 （IRD） 或金雀异黄素-丰富饮食 (GRD) 直到成年。测试不同年龄乳腺组织的增殖活性 (PCNA表达) 和成年去势动物乳腺组织对雌二醇 (E₂) 或金雀异黄素 （GEN）的雌激素敏感性并与不同的治疗方法进行对比。与IDD相比，在IRD和GRD 中E₂ 治疗导致乳腺组织的增殖和对雌激素反应明显降低。这一点关系到基因表达谱的改变和雌激素受体 α （ERα） 与β （ERβ） 比率的降低。

结论︰

我们的研究结果提供了证据证明在子宫内和产后接触富含 ISO或者GEN 的饮食，可以减少降低乳腺组织对雌激素的敏感性，并且支持在子宫内和产后 接触ISO 可以降低患乳腺癌的风险这一假设。