REGULATION OF ESTROGEN-RECEPTOR PROTEIN AND MESSENGER-RIBONUCLEIC-ACID BY ESTRADIOL AND PROGESTERONE IN RAT UTERUS

The objective of this study was to examine the mechanisms of estrogen receptor (ER) processing and replenishment in the uterus of ovariectomized rats after estradiol and progesterone treatment. Uterine ER binding activity, ER protein and ER mRNA were measured by receptor binding exchange assay, Western blot and slot blot, respectively. The regulation of ER levels in rat uterus by estradiol and progesterone was very dramatic. Changes in ER protein were faithfully reflected by changes in binding activity. Estradiol caused receptor ''processing'' within 4 h of administration followed by recovery or ''replenishment'' of ER levels to the initial level by 20 h. The term ''processing'' has previously been used to describe the loss of ER binding activity in the early phase of estradiol-action, but it was never clear whether the ligand binding site was inactivated by processing or if the receptor molecule actually disappeared. This study shows that receptor ''processing'' constitutes disappearance of receptor protein and the later ''replenishment'' phase represents new ER protein rather than recycling of ''processed'' receptor. Progesterone-action, on the other hand, influenced only the ''replenishment'' phase by blocking recovery of ER protein. ER mRNA was suppressed by estradiol at 8 h, after the receptor was ''processed'' and ''replenishment'' already initiated. Progesterone, on the other hand, did not alter the steady state level of the message. Other mechanisms, such as regulation of translation rate of existing mRNA and changes in the rate of degradation of ER proteins are more likely involved in acute regulation of ER by these ovarian steroid hormones.