Hormonal Control of Uterine Growth: The Effect of Hypothyroidism on Estrogen-Stimulated Cell Division

The increase in mitotic indices of uterine luminal epithelium, stroma, and myometrium were determined as a function of time after the administration of a single dose of 17β-estradiol to euthyroid and hypothyroid rats. Hypothyroidism reduced the increase in the mitotic index 5-fold in the luminal epithelium, 6-fold in the stroma, and 9-fold in the myometrium. In addition to reducing mitotic indices, hypothyroidism also produced a shift of 12 h in the time course of estrogen-stimulated cell division of all uterine cell types relative to euthyroid animals. This shift in the time course of cell division was preceded by a shift in the time course of uterine DNA synthesis measured by tritiated thymidine incorporation. In contrast, hypothyroidism did not alter the magnitude or the time course of synthesis of 2-deoxyglucose-6-phosphate from 2-deoxyglucose after estrogenic stimulation. These results indicate that hypothyroidism decreases the ability of all major uterine cell types to undergo cell division in response to acute administration of estradiol, and also shifts the time course of the uterine growthresponse to the hormone.