Interaction of estradiol with its receptor in the infertile Zucker fatty female rat

The biochemical and physiological characteristics of the uterine estrogen receptor (ER) were compared between lean and infertile, fatty rats of the Zucker strain. After ovariectomy, the amount of ER in the fatty rat uterus was less than half that found in the lean rat uterus. Also, following 5 or 11 daily injections of 10 µg estradiol-17β (E 2 ), the levels were significantly lower in the fatty rats. The equilibrium dissociation constants of the cytosol and nuclear ER were similar in both types of rats, as were the S values after sedimentation of the ER through 5-20% sucrose gradients. When nuclear translocation and cytosol replenishment of the uterine ER were examined, however, it was found that the peak of nuclear retention of the ER after an injection of E 2 occurred after 1 h in the lean rats and after 2 h in the fatty rats. Cytosol replenishment, moreover, was less in the fatty compared to the lean rats. The peak of nuclear ER retention correlated with the peak of in vivo uterine RNA synthesis as measured by a 1 h pulse of [ 3 H] uridine incorporation in vivo . The lean rats, however, also showed a second peak of incorporation occurring 8 h after E 2 injection. This second peak was not observed with the fatty rat. ER levels were also measured in the hypothalamus and anterior pituitary. Hypothalamic levels of the ER of fatty and lean rats were similar, but the fatty rat pituitaries had lower amounts of ER as compared to pituitaries from lean rats. Also, the wet weights of fatty rat pituitaries were lower than those from lean rats. Our data shows that the infertility in the Zucker obese rat is accompanied by physiological changes in the estradiol-receptor interaction in the uterus. Whether these changes contribute to the observed infertility is unknown at this time.