One of the first endocrine manifestations of reproductive aging in both rats and humans is an increase in the secretion of follicle-stimulating hormone (FSH). Furthermore, the type of FSH produced by the anterior pituitary gland (AP) seemingly is affected by the aging process of both species in that the AP's of older rats and humans contain proportionately more acidic FSH ishoromones than the AP's of their younger counterparts. Therefore, the major objective of the proposed research is to determine both the causes and consequences of age-related alterations in the secretion and production of FSH by the AP of female rats in hopes of providing valuable information regarding the etiology of hormonal imbalances associated with the human menopause. Specifically, the first series of studies will be designed to evaluate possible perturbations in the FSH-inhibin feedback loop as a consequence of the aging process since inhibin is important in regulating FSH secretion in young female rats. To this end, experiments will be proposed to evaluate the effects of aging on: 1) ovarian resposiveness to FSH with respect to inhibin production, and 2) the responsiveness of the hypothalamo-pituitary axis to inhibin. A second study will be conducted to determine whether increase in plasms FSH levels during estrus are due to an alteration in the basal (hypothalamic-independent) secretion rate of FSH from the AP. A third and final set of experiments will be designed to explore the possible consequences of an increase in FSH secretion with respect to aging of the reproductive axis. These studies will include an attempt to correlate possible age-related changes in the synthesis and/or secretion of estradiol-17Beta with the initial alterations in FSH secretion and production. Thus, by determining the genesis of increased FSH secretion and altered FSH production, it may be possible to disclose the initial perturbation in the reproductive axis which signals the onset of reproductive senescence in female rats. Moreover, since similar changes in FSH secretion and production are associated with the aging process in humans, the results of the proposed experiments will be extremely relevant to the clinical practitioner's understanding of the menopause. Finally, it is hoped that the data obtained from such studies may aid the gynecologist in developing a treatment which would effectively regulate the erratic nature of menstrual cycles normally observed during the menopausal transition.
| DePaolo, L V (1991) Hypersecretion of follicle-stimulating hormone (FSH) after ovariectomy of hypophysectomized, pituitary-grafted rats: implications for local regulatory control of FSH. Endocrinology 128:1731-40 |
| DePaolo, L V; Shimonaka, M; Schwall, R H et al. (1991) In vivo comparison of the follicle-stimulating hormone-suppressing activity of follistatin and inhibin in ovariectomized rats. Endocrinology 128:668-74 |
