Estrogenicity Of Soy Formula

大豆配方奶粉的雌激素作用

• 批准号: 7168873
• 负责人: WALTER ROGAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7168873
• 关键词: baby food; breast feeding; child physical development; clinical research; developmental nutrition; endocrine disorder; flavones; genistein; gestational age; hormone regulation /control mechanism; human milk; human subject; infant human (0-1 year); longitudinal human study; milk; nutrition related tag; nutritional epidemiology; phytoestrogens; soybeans

Genistein and daidzein are estrogenic isoflavones found in soybeans. Although they are about 1/10,000 as potent as estradiol, infants fed soy formula have serum concentrations that are up to 4 orders of magnitude higher than estradiol. Clinical trial data show increases in cholesterol synthesis consistent with an estrogen effect in infants fed soy formula vs. human milk or cow milk formula, and lowered response to polio vaccination, which might or might not be an estrogen effect. Anatomic, sonographic, and other biochemical evidence of estrogen exposure has not been looked for in infants fed soy. Whether such widely used products do or do not have clinically detectable estrogenic activity in infants, the group with the highest exposure per kilo, is important clinically; in addition, it may be a crucial test of the ability of laboratory measures of estrogenicity to predict actual endocrine response in humans. We have begun pilot studies to examine the natural history of estrogen responsive physiology in the newborn, and will use the results to develop a longitudinal study of the possible estrogenic effects of soy formula on infants. At the Boston Children?s Hospital, our collaborators in pediatric ultrasound have developed and assessed inter- and intra- rater reliability for examinations of the breast, uterus, ovaries, testes, prostate, adrenals, and thyroid. Using a protocol and eligibility criteria developed at NIEHS, by fall 2004 they will have examined 96 girls, ranging in age from less than 48 hours to one year, and 60 boys, ranging in age from less than 48 hours to 6 months. We find that the methods are reliable, ans that uterine and ovarian volume changes over time but that the endometrial stripe does not. Breast tissue and accompanying fat is readily imaged. At the Children?s Hospital in Philadelphia, our collaborators are doing physical examinations of the breasts and genitalia of 84 children total of both sexes ages from less than 48 hours to 6 months. This examination is a modification of the well-known Ballard scale for gestational age, which uses the degree of estrogen response by the breasts and genitals. The degree of estrogenization is so strongly related to gestational age that the weeks in utero for the child can be estimated using this examination. We find that breast tissue varies over time, and that fat is distinguishable from gland. We also find that vaginal wall cells are easy to collect, and that they appear to be estrogen responsive. In urine samples collected over the first year, isoflavone concentrations ar 3-5 orders of magnitude higher in children fed soy formula. Equol is not present. We have also collected samples at this site for analysis of a variety of hormones but are still developing methods. We are analyzing the physical examination, ultrasound, and isoflavone data now, and are beginning to plan the next study.

染料木黄酮和大豆黄酮是在大豆中发现的雌激素。虽然它们的效力约为雌二醇的1/10，000，但喂食大豆配方奶粉的婴儿的血清浓度比雌二醇高出4个数量级。临床试验数据显示，与母乳或牛奶配方相比，喂养大豆配方的婴儿胆固醇合成增加与雌激素效应一致，并且对脊髓灰质炎疫苗接种的反应降低，这可能是也可能不是雌激素效应。在食用大豆的婴儿中，尚未发现雌激素暴露的解剖学、超声学和其他生化证据。这些广泛使用的产品是否对婴儿（每公斤暴露量最高的群体）具有临床可检测的雌激素活性，在临床上很重要;此外，它可能是对实验室雌激素测定预测人类实际内分泌反应能力的关键测试。我们已经开始了初步研究，以检查新生儿雌激素反应生理学的自然史，并将利用研究结果对大豆配方奶粉对婴儿可能的雌激素效应进行纵向研究。 波士顿儿童？我们的儿科超声合作者已经开发并评估了乳腺、子宫、卵巢、睾丸、前列腺、肾上腺和甲状腺检查的评估者间和评估者内的可靠性。利用NIEHS制定的协议和资格标准，到2004年秋季，他们将检查96名女孩，年龄从不到48小时到一岁不等，60名男孩，年龄从不到48小时到6个月不等。我们发现这些方法是可靠的，子宫和卵巢的体积随时间变化，但子宫内膜条纹不随时间变化。乳房组织和伴随的脂肪很容易成像。 在孩子们？我们的合作者正在对84名儿童的乳房和生殖器进行体检，年龄从不到48小时到6个月。该检查是对众所周知的Ballard孕龄量表的修改，Ballard孕龄量表使用乳房和生殖器的雌激素反应程度。雌激素化的程度与胎龄密切相关，因此可以通过这项检查来估计胎儿在子宫内的周数。我们发现乳腺组织随着时间的推移而变化，脂肪和腺体是可以区分的。我们还发现阴道壁细胞很容易收集，而且它们似乎对雌激素有反应。在第一年收集的尿液样本中，大豆配方奶粉喂养的儿童的尿液浓度高出3-5个数量级。Equol不存在。我们还在该地点收集了样品，用于分析各种激素，但仍在开发方法。 我们现在正在分析体格检查、超声和MRI数据，并开始计划下一步研究。