Rimoldi Guillermo, Christoffel Julie, Seidlova-Wuttke Dana, Jarry Hubertus, Wuttke Wolfgang
Department of Clinical and Experimental Endocrinology, Georg-August-University, Göttingen, Germany.
Environ Health Perspect. 2007 Dec;115 Suppl 1(Suppl 1):62-8. doi: 10.1289/ehp.9367.
The isoflavone genistein (GEN) is found in soy (Glycine max) and red clover (Trifolium pratense). The estrogenic activity of GEN is known, and it is widely advertised as a phytoestrogen useful in alleviating climacteric complaints and other postmenopausal disorders. Knowledge of effects of long-term administration of GEN in laboratory animals is scarce, and effects in the uterus and mammary gland after long-term administration have not been studied. The uterus and mammary gland are known to be negatively influenced by estrogens used in hormone therapy.
We administered two doses of GEN [mean daily uptake 5.4 (low) or 54 mg/kg (high) body weight (bw)] orally over a period of 3 months to ovariectomized (ovx) rats and compared the effects with a treatment with two doses of 17beta-estradiol [E(2); 0.17 (low) or 0.7 mg/kg bw (high)]. Mammary glands, vaginae, and uteri were investigated morphologically and immunohistochemically. We quantified the expression of proliferating cell nuclear antigen (PCNA) and progesterone receptor (PR) in the mammary gland.
In rats treated with either of the E(2) doses or the high GEN dose, we found increased uterine weight, and histologic analysis showed estrogen-induced features in the uteri. In vaginae, either E(2) dose or GEN high induced hyperplastic epithelium compared with the atrophic controls. In the mammary gland, E(2) (either dose) or GEN increased proliferation and PR expression. Serum levels of luteinizing hormone were decreased by E(2) (both doses) but not by GEN.
In summary, E(2) and GEN share many effects in the studied organs, particularly in the vagina, uterus, and mammary gland but not in the hypothalamo/pituitary unit.
异黄酮染料木黄酮（GEN）存在于大豆（大豆属）和红三叶草（红车轴草属）中。GEN的雌激素活性是已知的，并且它作为一种植物雌激素被广泛宣传，对缓解更年期症状及其他绝经后疾病有用。关于在实验动物中长期给予GEN的影响的知识匮乏，长期给药后对子宫和乳腺的影响尚未得到研究。已知子宫和乳腺会受到激素疗法中使用的雌激素的负面影响。
我们对去卵巢（ovx）大鼠口服给予两剂GEN [平均每日摄入量为5.4（低）或54毫克/千克体重（bw）（高）]，持续3个月，并将其效果与给予两剂17β-雌二醇[E(2); 0.17（低）或0.7毫克/千克bw（高）]的治疗效果进行比较。对乳腺、阴道和子宫进行形态学和免疫组织化学研究。我们对乳腺中增殖细胞核抗原（PCNA）和孕激素受体（PR）的表达进行了定量分析。
在用任何一种E(2)剂量或高剂量GEN治疗的大鼠中，我们发现子宫重量增加，组织学分析显示子宫出现雌激素诱导的特征。在阴道中，与萎缩对照组相比，任何一种E(2)剂量或高剂量GEN均诱导上皮增生。在乳腺中，E(2)（任何一种剂量）或GEN均增加了增殖和PR表达。E(2)（两种剂量）均可降低血清促黄体生成素水平，但GEN无此作用。
总之，E(2)和GEN在研究的器官中具有许多共同作用，特别是在阴道、子宫和乳腺中，但在下丘脑/垂体单位中则没有。
