THE ROLE OF THE HYPOTHALAMIC-PITUITARY AXIS IN MENOPAUSE

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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.