Bolca S, Bracke M, Depypere H
Laboratory for Bioinformatics and Computational Genomics (Biobix), Faculty of Bioscience Engineering, Ghent University, Coupure links 653, B-9000 Ghent, Belgium.
Laboratory for Experimental Cancer Research, Department of Radiotherapy and Experimental Cancer Research, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium.
Facts Views Vis Obgyn. 2012;4(1):30-7.
In developed countries, the life expectancy of women is currently extending more than 30 years beyond the age of menopause. The menopausal transition is often associated with complaints. The conflicting results on the effectivity of phytoestrogens to alleviate menopausal symptoms. This discrepancy in treatment effect may be due to the large interindividual variation in isoflavone bioavailability in general and equol production in particular. Equol, a microbial metabolite of daidzein, has been hypothesized as a clue to the effectiveness of soy and its isoflavones, but only about 30-50% of the population harbor an intestinal microbial ecosystem supporting the conversion of daidzein into equol. There is much concern on breast cancer, since this incidence of this disease increases with age. There is indication that soy phytoestrogens may decrease this breast cancer incidence. In order to evaluate the estrogenic potential of these exposure levels, we studied the isoflavone-derived E2α- and E2β-equivalents (i.e. 17β-estradiol (E2)-equivalents towards ERα and ERβ, respectively) in human breast tissue. Total isoflavones showed a breast adipose/glandular tissue distribution of 40/60 and their derived E2β-equivalents exceeded on average 21 ± 4 and 40 ± 10 times the endogenous E2 concentrations in corresponding adipose and glandular biopsies, respectively, whereas the E2α/E2 ratios were 0.4 ± 0.1 and 0.8 ± 0.2 in adipose and glandular breast tissue, respectively. These calculations suggest that, at least in this case, soy consumption could elicit partial ERβ agonistic effects in human breast tissue. We are currently characterizing the differential activation of estrogen-responsive genes between dietary isoflavones, the chemopreventive selective ER modulators tamoxifen and raloxifene and exogenous estrogens in a controlled dietary intervention trial that integrates data on the exposure to estrogenically active compounds, expression of isoflavone and estrogen target genes, and epigenetic events. During the menopause, there is a close relation between the drop in serum estrogen and negative metabolic changes such as the increase in bone resorption and negative change in the serum lipid profile. Randomized controlled trials measuring bone turnover markers in menopausal women revealed that soy isoflavone supplements significantly but moderately decrease the bone resorption marker urinary deoxypyridinoline without significant effects on the bone formation markers serum bone alkaline phosphatase and osteocalcin.
在发达国家,女性的预期寿命目前比绝经年龄延长了30多年。绝经过渡通常伴随着各种不适症状。关于植物雌激素缓解更年期症状有效性的研究结果相互矛盾。这种治疗效果的差异可能是由于一般异黄酮生物利用度,尤其是雌马酚生成方面存在较大的个体间差异。雌马酚是大豆苷元的一种微生物代谢产物,被认为是大豆及其异黄酮有效性的一个线索,但只有约30%-50%的人群拥有支持大豆苷元转化为雌马酚的肠道微生物生态系统。人们对乳腺癌非常关注,因为这种疾病的发病率会随着年龄增长而增加。有迹象表明大豆植物雌激素可能会降低这种乳腺癌的发病率。为了评估这些暴露水平的雌激素潜力,我们研究了人乳腺组织中异黄酮衍生的E2α-和E2β-等效物(即分别针对雌激素受体α和雌激素受体β的17β-雌二醇(E2)等效物)。总异黄酮在乳腺脂肪/腺体组织中的分布为40/60,其衍生的E2β-等效物在相应的脂肪和腺体活检组织中平均分别超过内源性E2浓度的21±4倍和40±10倍,而在乳腺脂肪组织和腺体组织中E2α/E2比值分别为0.4±0.1和0.8±0.2。这些计算结果表明,至少在这种情况下,食用大豆可能会在人乳腺组织中引发部分雌激素受体β激动作用。我们目前正在一项对照饮食干预试验中,对饮食异黄酮、化学预防选择性雌激素受体调节剂他莫昔芬和雷洛昔芬以及外源性雌激素之间雌激素反应基因的差异激活进行特征描述,该试验整合了关于雌激素活性化合物暴露、异黄酮和雌激素靶基因表达以及表观遗传事件的数据。在绝经期间,血清雌激素下降与负性代谢变化密切相关,如骨吸收增加和血清脂质谱的负性变化之间存在密切关系。对绝经后妇女骨转换标志物进行测量的随机对照试验表明,大豆异黄酮补充剂可显著但适度降低骨吸收标志物尿脱氧吡啶啉,而对骨形成标志物血清骨碱性磷酸酶和骨钙素无显著影响。