Previous studies on female reproductive aging in rodents have demonstrated that a major manifestation of the onset of decline in fertility at midlife is the diminished uterine decidual cell response. This reaction is essential for zygote implantation and subsequent gestational success. Since the decidual cell response is under complex hormonal control by ovarian steroids (estrogen, E2, and progesterone, P) at least 2 causes of decline in this response leading to reduced fertility can be envisioned: 1) diminished output of E2 or P by the aging ovary, or 2) alteration in capacity of aging uteri to respond to steroid hormones. We plan to characterize plasma and uterine tissue concentrations of E2 and P by radioimmunoassay procedures in young and aging pregnant female mice in order to gain insight into whether reproductive decline in aging is associated with declining ovarian hormone levels. Additionally, since an absolute requirement exists for progesterone in insuring gestational success and because an important regulatory aspect of progesterone actions on the uterus appears to involve intracellular metabolism of this compound, we plan to characterize uterine P metabolism in young and aging mice. Preliminary evidence from this lab show a loss of uterine E2 receptors in aging rats and mice which could be substantially restored by injections of estradiol. Since E2 and P receptor proteins in uteri appear to be essential in the response of the uterus to steroids, we plan to study the regulation of uterine E2 and P receptors in aging pregnant mice. Given the inducibility of estrogen (and possibly progesterone) receptors by exogenous hormones, the uterus may provide a useful model system in which to study the control of hormone receptors during aging.