EFFECT OF OVARIAN SUPPRESSION ON PROTEIN METABOLISM

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 衰老与心脏病、糖尿病和身体残疾的风险增加有关。在女性中，这些与年龄有关的疾病的发病率在绝经后急剧增加。这导致了卵巢激素缺乏导致这些不良健康结果的假设。然而，卵巢激素缺乏本身对疾病和残疾风险因素的影响尚未明确界定。因此，本研究的主要目的是描述卵巢激素缺乏对葡萄糖、胰岛素、脂肪和蛋白质代谢的影响。 我们的总体假设是，卵巢激素缺乏改变底物周转和利用的方式，增加发展为慢性疾病和残疾的风险。具体而言，葡萄糖、胰岛素和脂肪代谢的改变增加了患心脏病和糖尿病的风险，蛋白质代谢的变化有助于减少瘦组织质量，这反过来又会促进残疾。为了证实我们的假设，我们将使用稳定同位素示踪法测量健康绝经前妇女在药物卵巢抑制前后的底物代谢。女性将随机接受促性腺激素释放激素激动剂醋酸亮丙瑞林或安慰剂。在治疗前和治疗开始后2个月，将在月经周期的卵泡期和黄体期进行底物代谢测量。 实验1将研究卵巢激素缺乏对血糖和胰岛素对高血糖反应的影响。实验2将研究在吸收后和肾上腺素刺激条件下，卵巢激素缺乏在全身脂解调节中的作用。实验3将研究在吸收后和模拟餐后条件下卵巢激素缺乏对全身蛋白质代谢的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aging is associated with increased risk for heart disease, diabetes and physical disability. In women, the incidence of these age-related conditions increases dramatically after menopause. This has led to the hypothesis that ovarian hormone deficiency contributes to these adverse health outcomes. However, the effect of ovarian hormone deficiency, per se, on risk factors for disease and disability has not been clearly defined. Thus, the primary goal of the proposed studies is to characterize the effect of ovarian hormone deficiency on glucose, insulin, fat and protein metabolism. Our overall hypothesis is that ovarian hormone deficiency alters substrate turnover and utilization in a manner that increases the risk for developing chronic disease and disability. Specifically, alterations in glucose, insulin and fat metabolism increase the risk for developing heart disease and diabetes and changes in protein metabolism contribute to reduced lean tissue mass which, in turn, promotes disability. To address our hypothesis, we will measure substrate metabolism using stable isotope tracer methodology in healthy, premenopausal women before and after pharmacological ovarian suppression. Women will be randomized to receive the gonadotropin-releasing hormone agonist leuprolide acetate or placebo. Measurements of substrate metabolism will be performed during both the follicular and luteal phases of the menstrual cycle prior to treatment and 2 months after the initiation of treatment. Experiment 1 will investigate the effect of ovarian hormone deficiency on the glucose and insulin response to hyperglycemia. Experiment 2 will examine the role of ovarian hormone deficiency in the regulation of whole-body lipolysis under postabsorptive and epinephrine-stimulated conditions. Experiment 3 will examine the effect of ovarian hormone deficiency on whole-body protein metabolism under postabsorptive and simulated-postprandial conditions.