CHANGES IN UTERINE ESTROGEN-RECEPTOR AND MORPHOLOGY IN AGING FEMALE RATS

Changes in uterine weight, morphology and estrogen receptor levels were studied in aging female rats. The uterine weight (534 ± 31 mg; mean ± SEM) in rats during early constant estrus at 12 months of age was comparable to that of young proestrous rats. A marked increase in uterine weight to 933 ± 135 mg occurred in late estrus at 24 months of age primarily as the result of an increase in the luminal fluid content. Histological examination of these uteri indicated the presence of tall proliferative luminal epithelium and thickened stromal and myometrial components, suggesting stimulation of the uterus by estrogen during constant estrus. A decrease in uterine weight to 344 ± 20 mg was observed in aging rats during persistent diestrus at 30 months of age. These uteri were characterized by low cuboidal luminal epithelia and secretory uterine stroma. Spontaneous formation of decidual tissue was also detected in some rats. These observations suggested that the uterine tissue in persistent diestrous rats was probably under progestin influence. Independent of the marked changes in uterine morphology in aging rats, an age related decrease in estrogen receptor content was detected in the uteri of the aging rats. Estrogen receptor content/uterus decreased with increasing age from 8.0 pmoles in young proestrous rats at 4 months to 4.5, 3.1 and 1.1 pmoles in rats at 12, 24 and 30 months of age, respectively. Expressed as estrogen binding sites/cell, a similar age related decrease in receptor concentration was observed in aging rat uterus with a decrease from 9,300 sites/cell at 4 months to 5,200, 3,700 and 2,200 sites/cell in aging rats at 12, 24 and 30 months of age, respectively. In contrast, no age related change in the dissociation constant of nuclear estrogen receptor was detected (Kd=1.4 ± 0.5 x 10-9 M). The present study demonstrates a decrease of uterine estrogen receptor content in female rats with advancing age. The marked decrease in uterine estrogen receptor in old rats may contribute to some adverse changes in uterine function resulting in an increased incidence of pregnancy failure.