Estrogen receptor replenishment. Evidence for receptor recycling

Replenishment of uterine estrogen receptor was examined in immature rats following injection of 16 alpha-estradiol. 16 alpha-Estradiol is a "short-acting" estrogen that, after a single injection, stimulates early estrogenic responses (water imbibition, induced protein synthesis, etc.), but not long term responses (DNA synthesis). Replenishment after 16 alpha-estradiol injection was complete within 4 h. Furthermore, disappearance of receptor from the nucleus closely corresponded to a reappearance of receptor in the cytoplasm. In contrast to this, receptor replenishment following injection of 1 microgram of either diethylstilbesterol or 17 beta-estradiol was very slow and lagged behind the disappearance of nuclear receptor, leading to an apparent decrease in total receptor content. Half-lives for the clearance of nuclear estrogen-receptor complexes were estimated to be 30 min for 16 alpha-estradiol and 2 h for 17 beta-estradiol, respectively. Inhibition of protein synthesis by cycloheximide did not inhibit replenishment after 16 alpha-estradiol injection. Studies on replenishment after 17 beta-estradiol injection in the presence of cycloheximide could not be interpreted due to a decrease in total receptor content caused by long term cycloheximide treatment. Multiple injections of 17 alpha-estradiol did not lead to a lag in replenishment time or a decrease in total receptor content. This represents a case in which estrogen receptor replenishment appears to be due entirely to receptor recycling.