Nuclear Receptor—Estrogen Complex: Relationship Between Concentration and Early Uterotrophic Responses1

Abstract

The quantitative relationship between the amount of receptor—estrogen complex in the nuclear fraction of rat uterine cells and the extent of early uterotropic responses was studied in the immature rat. The quantity of nuclear receptor—estrogen complex, R—E, is maximal 1 hr after estradiol treatment. A decrease in nuclear R—E between 1 and 6 hr following estradiol treatment was observed which was dependent on hormonal dosage. During this 5–hr period, 70–80% of the sites were lost from the nuclear fraction following pharmacologic doses (1.0–2.5 μg) while a 7–9% decrease was observed with physiological doses (0.05–0.1 μg). Maximal increases in uterine weight were obtained when levels of nuclear R—E represented only a fraction of the total quantity of receptor in the uterus. However, a high correlation was observed between water imbibition and the quantity of nuclear R—E present at 3 and 6 hr after estradiol injection. In addition, positive correlations were found between the quantity of nuclear R—E and the extent of water imbibition by the uterus 3 hr after the injection of estriol and estrone. These correlations suggest that the presence of the estrogen receptor in the nucleus may be involved in the induction of fluid uptake by the uterus. Maximal conversion of glucose to CO₂ was elicited by quantities of estrone, estradiol and estriol that were insufficient to result in maximal quantities of nuclear R—E in the uterus. Furthermore, 0.01 μg of estradiol results in an essentially maximal level of glucose oxidation at 6 hr after injection with no increase in nuclear R—E. This observation suggests that the nuclear R—E complex may not mediate the early glucose oxidation response. The results of this study indicate that cytoplasmic R is in excess of that required to obtain maximal uterotrophic responses and that responses are related to the fractional quantity of R—E that remains bound to the nucleus. (Endocrinology92: 1488, 1973)