AGING EFFECTS ON GONADOTROPIN STRUCTURE/FUNCTION

这个试点项目研究了生殖老化对 促性腺激素的结构和生物活性; 促黄体生成激素（LH）和促卵泡激素（FSH）。 的 维持雌性哺乳动物的生殖能力需要高度的 下丘脑、脑垂体和大脑皮层之间 腺体和卵巢。 正常水平和活动的调节 FSH和LH在维持卵巢功能方面至关重要。 生殖老化的特点是生育率逐渐下降， 不规则排卵周期的开始。 在老鼠和人类中， 这些与年龄相关的变化与血浆的改变模式有关 促性腺激素和卵巢类固醇生成的相关变化， 排卵 然而，虽然许多研究都集中在与年龄有关的 FSH和LH免疫反应性水平的改变， 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，显著影响 这些激素的生物效力。 FSH和LH是糖基化的 激素，N-连接的寡糖链连接在一个特定的 其主要氨基酸结构的方式。 寡糖 LH和FSH的组成受许多因素调节， 促性腺激素糖基化的变化会产生显著的影响 它们的生物活性。 尽管影响深远， 改变促性腺激素结构对它们的生物效力，稀疏 已经注意到糖基化的潜在变化， 促性腺激素在女性衰老过程中的生物活性。 这 因此，该项目将测试这一假设， LH和FSH结构和生物活性发生在 生殖老化，导致卵巢功能和年龄的改变- 与不孕症有关 具体而言，该试点项目将审查 结构和生物学上与年龄相关的潜在变化 排卵期间LH和FSH的储存和分泌形式的活性 中年大鼠的周期。 这些发现将为以下方面提供依据： 激素调节机制的深入研究 糖基化在老化过程中，并可能提供新的见解， 蛋白质结构改变在年龄相关性不育中的潜在作用 在女人身上。

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.