THE ROLE OF THE HYPOTHALAMIC-PITUITARY AXIS IN MENOPAUSE

下丘脑-垂体轴在更年期中的作用

• 批准号: 6050790
• 负责人: ABHIRAM SAHU
• 金额: $ 7.5万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-15 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6050790
• 关键词: Macaca mulatta; animal old age; biological models; female; female reproductive system; follicle stimulating hormone; growth /development; hormone regulation /control mechanism; hypothalamic pituitary adrenal axis; menopause; menstrual cycle; model design /development; ovariectomy; ovary; progesterone; radioimmunoassay; reproductive development; reproductive tissue transplantation

The goal of this project is to determine the extent to which hypothalamic mechanisms contribute to reproductive aging in higher primates. Menopause signals the cessation of reproductive function and may lead to the onset of variety of disorders associated with a deficiency in ovarian hormone secretion. While an intact hypothalamic-pituitary-ovarian axis is required for maintenance of normal menstrual cyclicity, considerable evidence suggests that menopause is the primary consequence of ovarian follicular loss. However, data are accumulating to argue that impaired hypothalamic activity contribute to reproductive decline in aging women. There is still no clear cut answer to the question of the precise degree to which the hypothalamus is involved in the development of the menopause in women. Since the rhesus monkey exhibits a menstrual cycle essentially similar to that of women and also shows the occurrence of menopause, this macaque appears to serve as an excellent animal model to address this question. Thus, we have proposed to ask the question of the involvement of the hypothalamic-pituitary axis in the development of menopause by transplanting ovaries of young to old animals. The Specific Aim is to establish a non-human primate model consisting of the aged female monkey bearing an ovarian transplant from a young donor in order to identify defects, if any, in the hypothalamic control of ovarian function during the menopause.This will be achieved by examining the effects of transplantation of young ovaries to old monkeys on menstrual cycles, and progesterone (P4) and follicle-stimulating hormone (FSH) levels in the recipients during the post-transplantation period. Ovarian transplantation will be conducted under sterile conditions by removing ovaries from young donors and transplanting them in subcutaneous pouches of the ovariectomized old monkeys. Menstrual cycles will be recorded from daily observations of vaginal bleeding, and plasma P4 and FSH levels will be determined by RIA. These studies will further our understanding of the biology of the menopause, and therefore will be relevant to the development of therapeutic approaches to the disorders associated with the menopause.

这个项目的目标是确定下丘脑机制在多大程度上有助于高等灵长类动物的生殖衰老。更年期标志着生殖功能的停止，并可能导致与卵巢激素分泌不足相关的各种疾病的发生。虽然维持正常的月经周期需要完整的下丘脑-垂体-卵巢轴，但大量证据表明绝经是卵巢卵泡丢失的主要后果。然而，越来越多的数据表明，下丘脑活动受损会导致老年妇女的生殖能力下降。下丘脑在女性更年期发展中的确切程度仍然没有明确的答案。由于恒河猴的月经周期基本上与女性相似，并且也显示出更年期的发生，因此该猕猴似乎是解决该问题的极好动物模型。因此，我们提出了通过将年轻动物的卵巢移植到老年动物来询问下丘脑-垂体轴参与更年期发展的问题。具体目的是建立一种非人灵长类动物模型，该模型由携带年轻供体卵巢移植的老年雌性猴组成，以确定绝经期下丘脑对卵巢功能的控制是否存在缺陷（如果存在）。这将通过检查年轻卵巢移植给老年猴对月经周期的影响来实现，以及移植后受体的孕酮（P4）和卵泡刺激素（FSH）水平。卵巢移植将在无菌条件下进行，从年轻供体中取出卵巢并将其移植到切除卵巢的老年猴的皮下袋中。将通过每日观察阴道出血记录月经周期，并通过RIA测定血浆P4和FSH水平。这些研究将进一步加深我们对更年期生物学的理解，因此将与更年期相关疾病的治疗方法的发展有关。