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

Abstract

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.