Occupied and unoccupied estrogen receptor during estrous cycle and pregnancy

Occupied and unoccupied forms of estrogen receptor (Re) were measured in hamster uterus during the estrous cycle and pseudopregnancy with a new assay method employing pyridoxal 5'-phosphate. In the cycle, occupied Re increased in cytosol and nuclear fractions in parallel with increasing serum estradiol during the follicular phase and then dropped sharply in both compartments during preovulatory progesterone secretion. Unoccupied Re occurred primarily in cytosol with low levels present in nuclei. It is pertinent that similar concentrations of occupied Re accumulate in cytosol and nuclear fractions, suggesting that occupied Re is distributed between these compartments according to an equilibrium model. Progesterone disrupts Re distribution through a selective action on the nucleus to downregulate occupied Re as was shown by progesterone treatment of the proestrous hamster. Re is chronically downregulated in the progesterone-dominated uterus, and the occupied form of Re recovers rapidly after progesterone withdrawal. Thus progesterone downregulates the Re system under physiological conditions by a selective action on the occupied form of Re in the target cell nucleus.