Differential contributions of ovarian and extraovarian factors to age-related reductions in plasma estradiol and progesterone during the estrous cycle of c57bl/6j mice

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.