Progesterone inhibition of uterine nuclear estrogen receptor: dependence on RNA and protein synthesis

Progesterone treatment was found previously to reduce nuclear estrogen receptor (Re) rapidly (2-4 hr) in the hamster uterus in vivo. The present study was done to determine whether this inhibitory effect of progesterone on uterine nuclear Re could be demonstrated in vitro ad whether progesterone action was dependent on RNA and protein synthesis. A uterine strip system was used in which estradiol pretretment caused cytosol Re translocation to the nucleus and increased synthesis of cytosol progesterone receptor (Rp) during a 16-hr incubation. When progesterone was added to the medium 4 hr before the end of the incubation, cytosol Rp was depleted and nuclear Re was greatly reduced. Further experiments done with actinomycin D, puromycin, and cycloheximide indicated that the progesterone-induced loss of uterine nuclear Re was dependent on RNA and protein synthesis. These results suggest that progesterone reduced nuclear Re through a mechanism involving Rp translocation and the induction of RNA and protein synthesis, a product of which is active in degrading or otherwise inactivating nuclear Re.