Characterization of uterine cytosol and nuclear sex steroid receptors in aging female ICR mice.

Changes in uterine wet weight and estrogen receptor levels were studied in aging female ovariectomized ICR mice. A marked increase in uterine wet weight was observed in 18-month-old mice after injection of estradiol-17 beta (E2), from 67.6 +/- 3.1 mg (control, no injection) to 98.2 +/- 14.8 mg (1 h after injection of 1.0 microgram E2) and to 125.2 +/- 15.8 mg (4 h after injection of 1.0 microgram E2). The response to E2 in old mice was greater than that in young. This observation suggests that the uteri of old mice are still sensitive to gonadal steroids up to the post-reproductive age of 18 months. A 2.7-fold age-related increase in uterine estrogen receptor content was also noted in aging ovariectomized female mice, from 0.38 pmol/uterus in young mice to 1.01 pmol/uterus in old mice (1 h after injection of E2). Both cytoplasmic estrogen receptor content and receptor concentration (expressed as estrogen binding sites/cell) increased with advancing age. In contrast, no age-related change in the dissociation constant of estrogen receptors was detected (Kd = 1.0 +/- 0.5 x 10(-9) mol/L). The progesterone receptor content also increased with advancing age. This study demonstrates a marked increase of uterine estrogen receptor content in aging mice, suggesting that the uterus is not responsible for the increased incidence of pregnancy failure in old mice.