Changes in Uterine Estrogen Receptor and Morphology in Aging Female Rats1

Abstract
Changes in uterine weight, morphology and estrogen receptor levles were studied. The uterine wt (534 .+-. 31 mg; mean .+-. SE) in rats during early constant estrus at 12 mo. of age was comparable to that of young proestrous rats. A marked increase in uterine wt to 933 .+-. 135 mg occurred in late estrus at 24 mo. 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 wt to 344 .+-. 20 mg was observed in aging rats during persistent diestrus at 30 mo. 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. 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 mo. to 4.5, 3.1 and 1.1 pmoles in rats at 12, 24 and 30 mo. 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 9300 sites/cell at 4 mo. to 5200, 3700 and 2200 sites/cell in aging rats at 12, 24 and 30 mo. of age, respectively. In contrast, no age related change in the Kd of nuclear estrogen receptor was detected (Kd = 1.4 .+-. 0.5 .times. 10-9 M). A decrease of uterine estrogen receptor content occurs 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.