EFFECT OF OVARIAN SUPPRESSION ON PROTEIN METABOLISM

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，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得到明确界定。因此，提出的研究的主要目的是表征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，卵巢激素缺乏改变了底物的周转和利用，从而增加了患慢性疾病和残疾的风险。具体来说，葡萄糖、胰岛素和脂肪代谢的变化增加了患心脏病和糖尿病的风险，蛋白质代谢的变化导致瘦组织质量减少，从而促进残疾。为了验证我们的假设，我们将使用稳定同位素示踪方法测量健康的绝经前妇女在卵巢药物抑制前后的底物代谢。妇女将随机接受促性腺激素释放激素激动剂醋酸leuprolide或安慰剂。底物代谢的测量将在治疗前和治疗开始后2个月的月经周期的卵泡期和黄体期进行。实验1将探讨卵巢激素缺乏对高血糖时葡萄糖和胰岛素反应的影响。实验2将检验卵巢激素缺乏在吸收后和肾上腺素刺激条件下对全身脂肪分解的调节中的作用。实验3将在吸收后和模拟餐后条件下研究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.