PROJECT 1 - ISOFLAVONES AND BONE HEALTH

几种类型的植物性产品含有芦荟酮正在销售作为替代雌激素替代疗法，以预防绝经后妇女的骨质疏松症。雌激素抑制骨吸收，并可能增加钙的吸收。雌马酮对骨骼健康的功效具有混合的结果，这可能取决于雌马酮的剂量和相互作用以及个体产生雌马酚的能力。具体目标1是确定染料木黄酮对雌马酚生产者和非雌马酚生产者绝经后妇女钙吸收和骨吸收的影响的剂量反应以及与其他大豆异黄酮的相互作用。我们将使用41 Ca，一种长寿命的同位素，来标记骨骼和加速器质谱（AMS）来监测饮食的扰动。这种研究骨吸收的创新方法是骨吸收的直接测量方法，与骨转换的生化标志物和传统的钙动力学相比，与研究骨密度变化相比速度更快，并且不像骨组织形态计量学那样具有侵入性。我们能够通过测量尿液中4lCa排泄的变化，系统地确定不同类型和剂量的含炔雌醇的植物产品在相同的绝经后妇女中依次抑制骨吸收的有效性的效果。初步证据表明，葛根，作为雌激素替代品销售，减少骨质流失，这可能涉及到一个不寻常的药物，葛根素。具体目标2是测量染料木黄酮、羟乙基纤维素和雌马酚对卵巢切除大鼠模型中骨和骨质量的剂量反应效应。具体目标3是研究大豆和大豆中异黄酮的代谢。我们已经发展了制备C-14和C-13标记的植物组织培养物的能力。通过将纯化或粗品组分灌胃给植入微透析探针的大鼠，我们可以跟踪生物活性化合物在整个身体中的代谢命运。 微量元素可以用AMS和microNMR进行追踪。

Several types of botanical products containing isoflavones are being marketed as an alternative to estrogen replacement therapy to prevent osteoporosis in postmenopausal women. Estrogen suppresses bone resorption and may increase calcium absorption. Efficacy of isoflavones on bone health has mixed results which may depend on the dose and interaction of isoflavones and the ability of individuals to produce equol. Specific Aim 1 is to determine the dose response of effect ofgenistein and the interaction with other soy isoflavones on calcium absorption and bone resorption in postmenopausal women who are equol vs. nonequolproducers. We will use 41Ca, a long-lived isotope, to label the skeleton and an Accelerator Mass Spectrometry (AMS) to monitor perturbations by diet. This innovative approach to study bone resorption is a direct measure of bone resorption in contrast to biochemical markers of bone turnover and traditional calcium kinetics, rapid compared to studying changes in bone density, and not invasive as is bone histomorphometry. We are able to systematically determine the effect of various types and dosages of isoflavone-containing botanical products sequentially in the same postmenopausal women for their effectiveness in suppressing bone resorption by measuring changes in 4lCa excretion in the urine. Preliminary evidence indicates that kudzu root, marketed as an estrogen replacement, reduces bone loss which may relate to an unusual isoflavone, puerarin. Specific Aim 2 is to measure the dose response effect ofgenistein, kudzu, and equol on bone and bone quality in an ovariectomized rat model. Specific Aim 3 is to study metabolism of isoflavones in soybeans and kudzu We have developed the ability to prepare C-14 and C-13 labled plant tissue culture. By gavaging purified or crude fractions to rats with implanted microdialysis probes, we can follow the metabolic fate of bioactive compounds throughout the body. Minute quantities can be traced with AMS and microNMR.