On the presence of nonfunctional uterine estrogen receptors in middle-aged and old C57BL/6J mice.

The nuclear binding kinetics of uterine 17 beta-estradiol (E2) receptors (UER) were studied throughout aging in intact and castrated (OVX) mice. When compared to young animals, 15- to 18-month-old mice showed a significant reduction in their total cytosolic (0.526 vs. 0.405 pmol/uterus; P less than 0.05) and nuclear (0.37 vs. 0.16 pmol/uterus; P less than 0.01) UER content, whereas the affinity (Ka) for estrogens remained constant (0.8-1.6 X 10(9) M-1). This age-related decrease in UER was preceded by a blunted and retarded nuclear binding of UER at 10-14 months of age, which was further accentuated after transition from perimenopause. Ovariectomy (OVX), whether performed neonatally or in adulthood, reduced the total concentration of cytosolic and nuclear UER in each age group studied, but did not prevent this reduced nuclear binding observed in middleaged mice. However, when standardized per tissue protein, the mean number of cytosolic UER from young and middle-aged, but not old, mice was reduced by 50% after neonatal OVX (176.5, 178.4, and 218.8 fmol/mg protein, respectively), whereas it remained unchanged when OVX was performed in adulthood and the animals subsequently studied at peri- and postmenopausal ages (326.3 and 283.3 fmol/mg protein, respectively). Daily administration of a physiological dose of E2 for 7 days to OVX mice of each age group induced maximal synthesis of UER in young animals, but not in peri- and postmenopausal ones; in peri- and postmenopausal animals, this was paralleled by reduced uterotropic responses despite similar increments in plasma E2. These results suggest an age-related, gonad-independent decline in the number of functional UER early in reproductive aging.