Abstract

The overall objectives of this study were to determine whether the rapid decrease in estrogen receptor (ER) binding in the rat uterus after an injection of estradiol and subsequent recovery of ER levels was accompanied by similar changes in ER mRNA levels. Furthermore, the effect of progesterone administered under conditions known to decrease ER binding, in the rat uterus, on ER mRNA levels was also investigated. Ovariectomy for 14 days brought about a 3-fold increase in rat uterine ER mRNA levels, and these elevated levels were decreased by a 3-day treatment with 2 mug of estradiol in ethanol/saline injected i.p. In the ovariectomized rat, 1 and 5 mug of estradiol brought about small but significant decreases in ER mRNA levels in 1 h, which did not parallel the rapid decrease in ER binding at that time reported earlier. The 10-mug dose of estradiol brought about a bigger decrease in ER mRNA levels. In the ovariectomized rat primed with estradiol (2 mug/day in ethanol/saline), the administration of 2 mug of estradiol brought about no change in uterine ER mRNA levels at 6 h as compared to the 1-h time point if the values were not corrected for beta-actin, which was significantly increased at 6 h. A dramatic increase in ER mRNA levels 12 h after the estradiol injection preceded the increase in ER binding observed at 18 h. Progesterone (0-8 mg/kg body weight [BW]) in the absence of estrogen priming brought about minimal but significant inhibition of ER mRNA levels 12 and 18 h after administration, with no effects at 1 and 6 h. In the presence of estrogen priming, the 0.8-mg/kg BW dose of progesterone did not cause any changes in ER mRNA levels beyond those brought about by estrogen alone after 1 h, even though it has been shown to significantly decrease ER binding. This was also true when a larger dose of progesterone (2.0 mg/kg BW) was used, a dose that decreases ER binding to a significantly greater extent than the 0.8-mg/kg BW dose. However, the 4.0-mg/kg BW dose of progesterone decreased ER mRNA levels. Thus a single injection of estradiol appears to cause a decrease in ER binding primarily by accelerated receptor processing and degradation with small changes in ER mRNA within the first hour. A significant increase in uterine ER mRNA at 12 h precedes increased ER binding at 18 h. This indicates new synthesis of ER during the recovery period. The effect of progesterone on the ER decrease does not appear to bc mediated via changes in ER mRNA levels, but appears to be manifested during post-transcriptional events including receptor processing and degradation.