The relative contributions of ovarian and extra-ovarian factors to the altered ovarian steroidal profiles of middle-aged mice were assessed by reciprocal, heterochronic ovarian grafting. Ovaries from cycling, young (2 months), and middle-aged (12 months) mice were exchanged by grafting under the renal capsules. Blood samples were obtained daily at midday throughout the estrous cycle for measurement of estradiol (E2) and 3-4 h after lights-out on proestrus to measure the preovulatory elevation of progesterone (P4). Middle-aged intact mice had lower mean concentrations of E2during the cycle, no detectable midday preovulatory elevation of E2, and an attenuated preovulatory increase of P4compared to young mice. Ovarian grafts from young donors failed to increase mean E2levels of middle-aged mice, but did restore the preovulatory elevation of E2and preovulatory P4to levels of young controls. Reciprocal grafting confirmed these findings: Ovaries from middle-aged donors in young hosts produced mean E2levels equivalent to those of young mice but were unable to support a preovulatory increase of E2or a preovulatory P4level equivalent to that of young controls. These results reveal differential contributions of ovarian and extra-ovarian factors to age changes in E2and P4. They indicate that ovarian aging plays an important role in attenuating the preovulatory increase of E2and P4, but extra-ovarian, presumably neuroendocrine, age changes underlie the mean reduction of E2levels across the estrous cycle.
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