Effects of aging on the hypothalamic-hypophyseal-gonadal axis in female rats

Abstract

The failure of reproductive function in aged rats could be due to deficiencies at the level of the ovary, pituitary, hypothalamus, or higher brain centers. The classic explanation that the ovary is depleted of follicles does not receive adequate support on the basis of histologic studies of aged ovaries. Basal serum gonadotropin levels change with increasing age in female rats. Serum follicle-stimulating hormone (FSH) levels rise while serum luteinizing hormone (LH) levels fall. Likewise, the characteristic response to castration is markedly altered in aged female rats with a reduced secretion of FSH and a minimal elevation of LH. However, the pituitaires of these animals are still caapable of responding to exogenous LH-releasing hormone with a delayed LH response whose magnitude simulates that seen in younger female animals. With increasing age there is decreased pituitary and/or hypothalamic sensitivity to the feedback action of estradiol. These data are consistent with the postulation that there is an altered hypothalamic-hypophyseal function in aged rats.

PIP: The hypothylamic-hypophyseal-gonadal axis in anovulatory retired breeder rats was evaluated to elucidate the changes occurring in aging female rats. Serum gonadotropins were measured and the response to castration and steroid replacement, ovarian responsiveness to exogenous gonadotropin stimulation, and pituitary responsiveness to luteinizing hormone-releasing hormone (LH-RH) determined. Castration and estradiol replacement in 22-month-old rats resulted in a reduced secretion of follicle stimulating hormone but at a lower rate than that seen in younger rats. The responses of serum LH to estradiol followed a similar pattern. Pregnant mare's serum gonadotropin given alone or combined with human chorionic gonadotropin in 22-month-old castrate rats caused a significant ovarian weight increase (p.01) over intact controls with a corresponding increase in uterine weight as well. Aging rats also responded to LH-RH (100 mg) with values of serum LH significantly elevated (p.01). These results suggest that the feedback mechanism of aging rats is less sensitive to stimulation than in younger rats. However, pituitaries are still capable of responding to stimulation. These data are consistent with the hypothesis of altered hypothalamic-hypophyseal function in aged rats.