FORMS OF GONADOTROPINS AS MARKERS OF MENOPAUSE

作为更年期标志的促性腺激素形式

• 批准号: 2769390
• 负责人: Steven Birken
• 金额: $ 28.99万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2769390
• 关键词: biomarker; clinical research; diagnosis design /evaluation; female; follicle stimulating hormone; hormone metabolism; hormone regulation /control mechanism; human subject; hybridomas; immunologic assay /test; laboratory mouse; luteinizing hormone; menopause; monoclonal antibody; postmenopause; urinalysis; women's health

With the extension of the human life span, women spend a third of their lives beyond the reproductive years. The transition into menopause is associated with physical risks and psychological adjustments. Major research initiatives are currently under way to improve understanding of these of these changes but these efforts are hampered by the hampered by the lack of diagnostic tools for determining how close a woman is to menopause. If a reliable test existed to differentiate a premenopausal woman from a woman early in menopause, new research initiatives would be posible since menopausal changes could be placed in relation to the stage of the menopusal transition. Such a test would also help diagnose patients whose symptoms are dissociated from current critria as FSH levels, women who have no uterus and thus no menses by which to gauge menopause, and as a possible guide to estrogen replacement dosing. We propose a novel approach of developing urinary assays to determine how close a woman is to menopause based on the excreted metabolities of the beta subunits of hLH and hFSH. Heterodimeric gonadotropins are not stable in urine but these metabolites are highly stable, without any additives, to storage and freeze-thaws. Based on our experiences with the diagnostic utility of urinary metabolites of hCG and new findings (reported in this application) on metabolites of hLH, we propose to develop tools to measure FSH urinary metabolites and use these immunogical tools, along with those hLH, to test the hypothesis that measurement of excreted metabolites of FSH may provide better markers of the entry into menopause than does the current unreliable marker of serum FSH concentration. We propose to: 1. Isolate and characterize the beta subunit fragments of FSH from the urine of postmenopausal women. 2. Develop specific monoclonal antibodies to FSH metabolites and two site immunoassays for measuring the FSH metabolites in urine. 3. Test applicability of measurement of LH and FSH fragments as markers of the onset of menopause and as response markers to estrogen replacement therapy.

随着人类寿命的延长，女性花费了三分之一的时间 他们的寿命超过了生育年龄。 过渡到 更年期与身体风险和心理风险有关 调整。 目前正在进行重大研究举措 提高对这些变化的理解，但这些努力是 由于缺乏诊断工具而受到阻碍 确定女性距离更年期有多近。 如果测试可靠的话 存在的目的是将绝经前女性与早期女性区分开来 在更年期，新的研究举措将是可能的，因为 更年期的变化可以与所处的阶段相关 更年期过渡。 这样的测试也有助于诊断患者 其症状与当前 FSH 水平标准无关， 没有子宫，因此没有月经来衡量的女性 更年期，并作为雌激素替代剂量的可能指南。 我们提出了一种开发尿液检测的新方法 根据排泄物确定女性距离更年期有多近 hLH 和 hFSH β 亚基的代谢。 异二聚体 促性腺激素在尿液中不稳定，但这些代谢物高度 稳定，不含任何添加剂，耐储存和冻融。 基于 我们在尿液代谢物的诊断用途方面的经验 hCG 和有关代谢物的新发现（本申请中报告） hLH，我们建议开发测量 FSH 尿代谢物的工具 并使用这些免疫学工具以及 hLH 来测试 假设测量 FSH 排泄代谢物可能 提供比更年期更好的进入更年期标志 目前血清 FSH 浓度的不可靠标记。 我们建议 1. 分离并表征 FSH 的 β 亚基片段 来自绝经后妇女的尿液。 2.制定具体的 FSH 代谢物单克隆抗体和二位点免疫测定 用于测量尿液中的 FSH 代谢物。 3. 测试适用性 测量 LH 和 FSH 片段作为疾病发生的标记 更年期和作为雌激素替代疗法的反应标志物。