Regulation of the Uterine Response to Estrogen by Thyroid Hormone*

Abstract
After estradiol (E2) administration, early increases (within 4 h) in uterine wet weight and the synthesis of 2-deoxyglucose-6-phosphate from 2-deoxyglucose were similar in ovariectomized rats and in ovariectomized rats made hypothyroid by feeding a low I diet containing propylthiouracil. Most late uterine responses occurring 24 h after E2 treatment were greatly diminished in the hypothyroid animals. The diminished responses included increases in uterine wet weight, dry weight, protein content, RNA content and the incorporation of thymidine into uterine DNA. One response, the synthesis of 2-deoxyglucose-6-phosphate from 2-deoxyglucose was not diminished in hypothyroid rats 24 h after E2 treatment. The diminished uterine response was not due to a shift in the dose-respone curve for E2, but resulted from a decrease in the magnitude of the maximum uterine response. Treatment of hypothyroid rats with exogenous T3 [triiodo thyronine] restored the diminished uterine response in a dose- and time-dependent manner. A dose of 0.5 .mu.g T3/100 g BW [body wt] for 5 days restored the response completely, while 48-72 h of treatment with higher doses of T3 were required to restore the response. The effect of T3 was not mediated by the pituitary, since exogenous T3 restored diminished uterine responses in ovariectomized, hypophysectomized animals. Thyroid hormones may have a direct effect on the uterus which regulates the responsiveness of the organ to E2.