Restoration of ovulatory cycles by young ovarian grafts in aging mice: potentiation by long-term ovariectomy decreases with age.

The relative contributions of ovarian and hypothalamic-pituitary factors to the anovulatory status of aging mice were evaluated by measuring the capacity of mice to resume ovulatory cyclicity after receiving young ovaries under the renal capsule. Young grafts partially restored cyclicity if old hosts were acutely ovariectomized but almost fully restored cyclic ovulatory function if the old hosts had been ovariectomized early in adulthood. With advancing age, however, the efficacy of the grafts declined progressively in both acute and long-term ovariectomized groups. These data show that both ovarian and hypothalamic-pituitary aging contribute to the etiology of anovulation. Although chronic withdrawal from ovarian secretions retards the age of onset of hypothalamic-pituitary aging, the duration of this ameliorative effect is limited by progressive ovary-independent neuroendocrine dysfunction.