Regulation of Uterine Responsiveness to Injected Estradiol in Nutritionally Stressed Ovariectomized Rats by Adrenal-Derived Estradiol*

Abstract

The effects of diet composition and starvation on the inducibility by estradiol of uterine glucose-6-dehydrogenase (G6PD) activity in mature ovariectomized rats has been evaluated. Starvation for 5 days and feeding a purified protein-free diet for 3 days caused a maximal increase in the inducibility of uterine G6PD activity relative to animals fed a basal diet. Inducibility of the enzyme was decreased as the amount of casein in the diet was increased from 0–45% and refeeding protein began to reverse the effect of protein deprivation on the inducibility of the enzyme within 24 h. The basal level of uterine G6PD activity was unchanged by diet or starvation, and the increased inducibility by estradiol in starved and/or proteindeprived rats was due to a 2-fold increase in the relative de novo rate of G6PD synthesis. The uterine binding and retention of [3H]estradiol given in vivo was increased by 40% in starved and/ or protein-deprived rats, and this increase appeared to be due to an increase in the estradiol receptor content of the uterus in the nutritionally deprived animals. Measurement of plasma estradiol levels revealed the presence of 12.7, 32.8, and 34.3 pg/ml in rats which were fed basal or protein-free diets or which were starved, respectively. The inducibility of uterine G6PD activity by estradiol was found to be statistically correlated with plasma estradiol levels before injection of exogenous steroid at r = 0.95 (P < 0.01), with cytosol estradiol receptor levels at r = 0.69 (P < 0.05), and with nuclear estradiol receptor levels at r = 0.86 (P < 0.01). The plasma estradiol levels appear to increase due to increased adrenal activity, since the dietary treatments caused increased adrenal weight and a decrease in thymus weight and adrenal suppression by administration of dexamethasone caused plasma estradiol levels in all groups to be suppressed and abolished the effect of starvation or a protein-free diet on the induciility of uterine G6PD. These results suggest that the uterine response to estradiol in starved and protein-deprived ovariectomized mature rats is increased due to elevated circulating levels of adrenalderived estradiol and that increased levels of plasma estradiol over the range of 13–35 μg/ml regulate uterine estradiol receptor levels in the uterus without initiating a complete uterine response. The magnitude of the uterine response after injection of estradiol appears to be directly related to the amount of estradiol receptor in the tissue.