Dietary soy effects on mammary gland development during the pubertal transition in nonhuman primates.

Dietary soy effects on mammary gland development during the pubertal transition in nonhuman primates.
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DOI:
10.1158/1940-6207.capr-13-0128
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发表时间:
2013-08
期刊:
Cancer prevention research (Philadelphia, Pa.)
影响因子:
--
通讯作者:
Cline JM
Cline JM
中科院分区:
其他
文献类型:
--
作者:
Dewi FN;Wood CE;Lees CJ;Willson CJ;Register TC;Tooze JA;Franke AA;Cline JM

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虽然流行病学研究表明,在生命早期摄入大豆可能会降低患乳腺癌的风险,但也有人担心,儿童时期摄入大豆异黄酮可能会改变青春期发育和激素水平。在这里,我们在非人灵长类动物模型中评估了高大豆饮食对青春期乳房发育、性激素和生长的影响。在大约4.5年的时间里,雌性食蟹猴随机接受一种典型的北美饮食,其中含有两种蛋白质来源之一:1)酪蛋白/乳清蛋白(CL, n=12,作为对照)或2)大豆分离蛋白,其中含有相当于人类剂量的120毫克/天异黄酮(soy, n=17),这相当于大约四份大豆食品。青春期接触大豆饮食没有改变月经初潮的开始,生长和青春期进展的指标,或循环雌二醇和黄体酮浓度。在4次月经后超声检查的第一次中,大豆组子宫内膜面积更大(P<0.05)。饮食对乳腺分化有微妙的影响,初潮后大豆组分化的大小叶单位数量较多,未成熟导管比例较低(P<0.05)。小小叶和顶芽的数量以及乳腺上皮细胞的增殖不受饮食的影响。黄体酮受体在大豆饲料动物未成熟小叶中的表达较低(P<0.05)。我们的研究结果表明,在月经初潮之前开始食用大豆可能会导致适度的影响,这与成年后更分化的乳房表型相一致。
While epidemiologic studies suggest that soy intake early in life may reduce breast cancer risk, there are also concerns that exposure to soy isoflavones during childhood may alter pubertal development and hormonal profiles. Here, we assessed the effect of a high-soy diet on pubertal breast development, sex hormones, and growth in a nonhuman primate model. Pubertal female cynomolgus monkeys were randomized to receive a diet modeled on a typical North American diet with one of two protein sources for ~4.5 years: i) casein/lactalbumin (CL, n=12, as control) or ii) soy protein isolate with a human equivalent dose of 120 mg/day isoflavones (SOY, n=17), which is comparable to approximately four servings of soy foods. Pubertal exposure to the SOY diet did not alter onset of menarche, indicators of growth and pubertal progression, or circulating estradiol and progesterone concentrations. Greater endometrial area was seen in the SOY group on the first of 4 postmenarchal ultrasound measurements (P<0.05). There was a subtle effect of diet on breast differentiation whereby the SOY group showed higher numbers of differentiated large-sized lobular units and a lower proportion with immature ducts following menarche (P<0.05). Numbers of small lobules and terminal end buds and mammary epithelial cell proliferation did not differ by diet. Expression of progesterone receptor was lower in immature lobules of soy-fed animals (P<0.05). Our findings suggest that consumption of soy starting before menarche may result in modest effects consistent with a more differentiated breast phenotype in adulthood.