AGING EFFECTS ON GONADOTROPIN STRUCTURE/FUNCTION

衰老对促性腺激素结构/功能的影响

• 批准号: 2706017
• 负责人: PHILIP S LAPOLT
• 金额: $ 6.79万
• 依托单位: CALIFORNIA STATE UNIVERSITY LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-15 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2706017
• 关键词: aging; female; female reproductive system; follicle stimulating hormone; glycosylation; gonadotropins; hormone regulation /control mechanism; laboratory rat; luteinizing hormone; protein structure function; radioimmunoassay; reproduction

This pilot project examines potential effects of reproductive aging on the structure and biological activity of the gonadotropin hormones; luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The maintenance of reproductive competence in female mammals requires highly integrated feedback interactions between the hypothalamus, the pituitary gland, and the ovary. The regulation of normal levels and activities of FSH and LH is critical in maintaining ovarian functions. Reproductive aging is characterized by gradually declining fertility and the onset of irregular ovulatory cycles. In both rat and human species, these age-related changes are associated with altered patterns of plasma gonadotropins, and related changes in ovarian steroidogenesis and ovulation. However, while many studies have focused upon age-related alterations in the immunoreactive levels of FSH and LH in the circulation, increasing evidence indicates that changes in gonadotropin protein structure may occur as well, significantly influencing the biological potency of these hormones. FSH and LH are glycosylated hormones, with N-linked oligosaccharide chains attached in a specific manner to their primary amino acid structure. The oligosaccharide composition of LH and FSH is regulated by a number of factors, and changes in the glycosylation of gonadotropins can have dramatic effects on their biological activity. However, despite profound effects of altered gonadotropin structure on their biological potencies, sparse attention has been paid to potential changes in glycosylation and biological activity of gonadotropins during aging in females. This project will therefore test the hypothesis that alterations in the structure and biological activity of LH and FSH occur during reproductive aging, contributing to altered ovarian function and age- related infertility. Specifically, this pilot project will examine potential age-related changes in structure and biological activity of stored and secreted forms of LH and FSH during the ovulatory cycle in middle-aged rats. These findings will provide the basis of future in-depth studies on the mechanisms regulating hormone glycosylation during aging, and may provide new insights into the potential role of altered protein structure in age-related infertility in women.

该试点项目研究了生殖衰老对 促性腺激素的结构和生物活性； 黄体生成素（LH）和卵泡刺激素（FSH）。 这 维持雌性哺乳动物的生殖能力需要高度 下丘脑、垂体之间的综合反馈相互作用 腺体和卵巢。 正常水平和活动的调节 FSH 和 LH 对维持卵巢功能至关重要。 生殖衰老的特点是生育能力逐渐下降， 排卵周期不规则的开始。 在老鼠和人类中， 这些与年龄相关的变化与血浆模式的改变有关 促性腺激素，以及卵巢类固醇生成的相关变化和 排卵。 然而，尽管许多研究都集中在与年龄相关的 FSH 和 LH 免疫反应水平的变化 循环，越来越多的证据表明促性腺激素的变化 蛋白质结构也可能发生，显着影响 这些激素的生物效力。 FSH 和 LH 被糖基化 激素，具有连接在特定位置的 N-连接寡糖链 其主要氨基酸结构的方式。 低聚糖 LH 和 FSH 的组成受多种因素调节，并且 促性腺激素糖基化的变化会产生巨大的影响 关于它们的生物活性。 然而，尽管影响深远 改变促性腺激素结构对其生物效力的影响，稀疏 人们已经注意到糖基化的潜在变化和 女性衰老过程中促性腺激素的生物活性。 这 因此，项目将检验以下假设： LH 和 FSH 的结构和生物活性发生在 生殖衰老，导致卵巢功能改变和年龄增长 相关的不孕症。 具体来说，该试点项目将审查 潜在的与年龄相关的结构和生物学变化 排卵期间储存和分泌的 LH 和 FSH 的活性 中年大鼠的周期。 这些发现将为 未来对激素调节机制的深入研究 衰老过程中的糖基化，可能提供新的见解 蛋白质结构改变在年龄相关不孕症中的潜在作用 在女性中。