Cryptic estrogen binding protein complicates analysis of estrogen receptor distribution

The response of rat uterine estrogen receptor sub-species to injection of 5 micrograms estradiol has been investigated in intact and 4-weeks' ovariectomized adult animals. Determinations of occupied and unoccupied receptor subcellular fluctuations reveal significant differences not detectable under standard assays which measure only total nuclear and unoccupied cytosolic receptors. Both animal models manifest a high level of unoccupied nuclear receptors which are inaccessible to estrogen. In contrast to the intact animal, uteri from castrate animals have a high level of occupied receptors in the cytosol, which remains high following estrogen exposure. Receptor processing occurs in the castrate, but not the intact, animal. The results demonstrate that traditional assays are complicated by the presence and simultaneous measurement of non-responsive receptor species which quantitatively differ widely among animal models and will give rise to an erroneous interpretation of the pattern of estrogen-induced turnover of its receptor.