Unbound Progesterone Receptors Are in Equilibrium between the Nucleus and Cytoplasm in Cells of the Rat Uterus*

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Abstract
The classical model for the mechanism of action of steroids holds that unbound receptors for steroids reside exclusively in the cytoplasmic compartment and that they undergo translocation to the nucleus when bound to steroids in a process which is temperature sensitive. We have in the past proposed that unbound receptors for estrogen are in both nucleus and cytoplasm in a state of equilibrium. In the present study we looked at the location of the progesterone receptor using autoradiography and biochemical procedures. Uteri were incubated with [3H]progesterone or [3H]R5020 (dimethyl-19-nor-pregna-4,7-diene-3,20 dione, 17α,21-[17α-methyl-3H]) for 5 min at 4 C. When the tissue was processed for autoradiography, the localization of steroid was nuclear. In contrast, when the tissue was processed using the usual biochemical procedures, all binding activity appeared in the cytoplasm. In addition, when concentrated preparations of homogenized uteri were made, free receptor could be demonstrated in the crude nuclear preparations. We hypothesize that unbound progesterone receptor, like unbound estrogen receptor in the rat uterus, is in both the nucleus and cytoplasm of cells. In addition, we propose that the intracellular distribution of unbound receptors for all steroids is dependent upon the equilibrium conditions present.