Contribution of the Ovary Versus Hypothalamus-Pituitary to Termination of Estrous Cycles in Aging Rats Using Ovarian Transplants1

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Abstract
Vaginal smear patterns were monitored for 80 days after orthotopic ovarian transplants (OvTr) between young and old rats to examine the importance of the ovary and the hypothalamus-pituitary in the termination of estrous cyclic activity. At the end of this period, the rats were sacrificed at 2200 h, blood was collected for measurement of ovarian steroids and gonadotropin, and ovaries were prepared for histolgoical study. A 2nd experiment examined the effect of a reduction in ovarian tissue by unilateral ovariectomy of old rats on estrous cyclicity during the first 16 days following surgery. During the 80 days of observation, 25% of the old and 0% of the young sham-operated rats showed irregular estrous cycles. This decrease in cyclicity followed a decrease in the total number of oocytes in the ovaries. Rats with OvTr did not cycle as regularly as young or old intact rats; and 75% of both young and old recipients with OvTr were acyclic by Day 80. Ovarian factors were implicated in the termination of cyclicity since: old ovaries in either old or young recipients had a limited ability to maintain cyclicity compared to young or prepuberal ovaries: rats with OvTr which continued to cycle had more ovarian tissue and oocytes than rats which had become constantly estrous or anestrous, but fewer oocytes than intact rats; and in Experiment 2, a greater number of old unilaterally ovariectomized rats demonstrated irregular cycles by 16 days after surgery compared to old intact rats. Within the group of acyclic rats with OvTr, more (P < 0.05) old than young recipients became constantly estrous, while more young than old recipients became anestrous. Since numbers of follicles were not different between rats with constant estrus and anestrus, this suggested that there also were alterations at the hypothalamic-pituitary axis with advancing age. As long as cyclicity was maintained, there were no significant differences in serum concentrations of the 6 measured steroids or prolactin at 2200 h on metestrus between intact rats and rats with OvTr. However, compared to intact rats, concentrations of luteinizing hormone (LH) and FSH were increased in the cycling rats with OvTr. A further increase in LH and FSH occurred during constant estrus, with castration levels found in anestrous rats. The increase in gonadotropins and the decrease in estrous cyclic activity accompnaied a decrease in the number of growing follicles. This increase in gonadotropins cannot be explained by changes in steroids alone, since a significant decline in ovarian steroids was not found at this particular sampling time, except in rats with OvTr which were anestrous. A reduced amount of ovarian tissue and number of follicles apparently plays a major role in the decline in reproductive function, probably through a reduction in inhibin. However, some difference at the hypothalmic-pituitary axis is responsible for the increased incidence of constant estrus in older rats.