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: 2467877
• 负责人: Steven Birken
• 金额: $ 27.81万
• 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/2467877
• 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 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。 目前正在开展重大研究活动， 提高对这些变化的理解，但这些努力 由于缺乏诊断工具， 判断一个女人离更年期有多近 如果一个可靠的测试 存在区分绝经前妇女和早期妇女的方法 在更年期，新的研究举措将是可能的，因为 绝经期的变化可能与绝经期的阶段有关。 过渡期。 这样的测试也将有助于诊断患者 其症状与FSH水平的当前critria无关， 女性没有子宫，因此没有月经来衡量 绝经期，并作为一个可能的指导雌激素替代剂量。 我们提出了一种新的方法，发展尿液分析， 根据女性的排泄物来判断她离更年期有多近 hLH和hFSH的β亚基的代谢。 异二聚体 促性腺激素在尿中不稳定，但这些代谢物高度 稳定，不含任何添加剂，储存和冻融。 基于 我们的经验与尿代谢物的诊断效用， 人绒毛膜促性腺激素和关于代谢物的新发现（本申请中报告） hLH，我们建议开发工具来测量FSH尿代谢产物 并使用这些免疫学工具，沿着那些hLH，来测试 假设FSH分泌代谢物的测量可能 提供了更好的进入更年期的标志物， 目前不可靠的血清FSH浓度标志物。 我们提出 至：1. 分离和鉴定FSH β亚基片段 从绝经后妇女的尿液中提取的 2. 制定具体 抗FSH代谢物单克隆抗体和双位点免疫测定 用于测量尿液中的FSH代谢物。 3. 测试适用性 测量LH和FSH片段作为发病的标志物 绝经和作为雌激素替代疗法的反应标志物。