Inhibitory Effect of Progesterone on Occupied Estrogen Receptors of Anterior Pituitary and Uterus in Adult Rats

Abstract

The acute effects of a single progesterone injection on estradiol receptor (E(2)R) binding in the anterior pituitary and uterus were examined in the mature ovariectomized rat. Adult ovariectomized female rats receiving estradiol were injected with various doses of progesterone followed 1 h later by a final injection of 2 mug of estradiol. All animals were sacrificed 1 h after estradiol and the E(2)R binding in the nuclei and cytosol was determined. In the anterior pituitary, progesterone decreased total nuclear E(2)R in a biphasic inhibitory pattern, with maximal effects at 0.8 and 4 mg/kg body wt doses of progesterone and a smaller decrease with the 2 mg/kg body wt dose. This progesterone-induced decrease of nuclear E(2)R was due to a decrease in the occupied form of nuclear E(2)R. The unoccupied nuclear E(2)R and cytosol E(2)R binding were not altered by progesterone administration. In the uterus, progesterone caused a dose-dependent decrease in total nuclear E(2)R binding. This effect also occurred in the occupied form of E(2)R. The uterine unoccupied nuclear E(2)R and cytosol E(2)R were not altered by progesterone administration. These studies emphasize differences in the tissue specificity of progesterone action on occupied nuclear E(2)R which are presumably responsible for the mediation of estradiol action, and provide a biochemical basis for our previous observations of multiphasic effect of progesterone on gonadotropin secretion.

Changes in Rat Uterine Estrogen Receptor Messenger Ribonucleic Acid Levels during Estrogen- and Progesterone-Induced Estrogen Receptor Depletion and Subsequent Replenishment1

“…Previous studies from our laboratory have demonstrated a dose-dependent decrease in occupied nuclear uterine ER in estrogen-primed, ovariectomized rats treated with either progesterone or 5a-dihydroprogesterone [11,22]. Dramatic decreases in uterine ER binding have also been observed after a single injection of estradiol by several investigators who have shown replenishment of the binding activity in 16-24 h [3, 6, 7, 23-25].…”

“…In the estrogen-primed, ovariectomized rat, injection of 0.8 mg/kg BW of progesterone 1 h before the final estradiol injections brings about a significant decrease in ER binding [11]. Progesterone administration followed by an estradiol injection resulted in no change in ER mRNA levels at the 1-h time point as compared to the results when estradiol was administered in the absence of progesterone (Fig.…”

“…Studies by Fuentes et al [11] demonstrated a dose-dependent depletion of ER by progesterone in the estrogenprimed, ovariectomized immature rat uterus 1 h after a final estradiol injection. Therefore, ER mRNA levels were studied in this model in which 0.8, 2.0, and 4.0 mg/kg BW of progesterone were used.…”

“…All animals were killed 1, 6, 12, or 18 h later and the uteri were collected for ER mRNA determination. The doses of steroids used and the injection paradigm employed was adopted from Fuentes et al [11] who measured ER binding under identical conditions 1 h after the final estradiol injection. Experiment 6.…”

“…Likewise, it is not known whether the delay in replenishment of the ER after a single injection of estradiol is due to the inhibition of new ER synthesis. Furthermore, the administration of progesterone has been found to bring about a decrease in occupied nuclear ER in the uterus by a number of investigators [8][9][10][11]. It is not known whether this action of progesterone on the ER is due to accelerated processing of the ER or inhibition of new ER synthesis.…”