THE ROLE OF THE HYPOTHALAMIC-PITUITARY AXIS IN MENOPAUSE

该项目的目标是确定下丘脑机制在多大程度上促进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，下丘脑活动受损是老年女性生殖能力下降的原因之一。下丘脑在多大程度上参与了女性更年期的发展，这一问题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，而且也显示了更年期的发生，因此这只猕猴似乎是解决这个问题的一个很好的动物模型。因此，我们提出了通过将幼年动物的卵巢移植到老年动物的卵巢来探讨下丘脑-垂体轴参与更年期发育的问题。本研究的具体目的是建立一个非人类灵长类动物模型，该模型由一只年轻供者进行卵巢移植的老年雌性猴子组成，以确定更年期期间下丘脑对卵巢功能的控制是否存在缺陷。这将通过检测年轻卵巢移植给老年猴子对月经周期的影响以及移植后受者体内孕酮(P4)和卵泡刺激素(FSH)水平来实现。卵巢移植将在无菌条件下进行，方法是从年轻捐赠者身上摘除卵巢，然后将它们移植到去卵巢的老年猴子的皮下囊中。月经周期将通过每天观察阴道出血来记录，血浆P4和FSH水平将通过放射免疫法测定。这些研究将进一步加深我们对更年期生物学的理解，因此将与开发与更年期相关的疾病的治疗方法有关。

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.