Cytosol and Nuclear Compartmentalization of Progesterone Receptors of the Rat Uterus*

Exchange of [3H]progesterone for progesterone bound in vivo to nuclear progesterone receptors (Rn)of rat uterus was accomplished by overnight incubation at 4 C. The Rnwere similar to cytosol progesterone receptors (Rc) in specificity, N-ethylmaleimide sensitivity, and Kd. Uterine Re and Rnwere measured after progesterone injection in adult rats ovariectomized on day 0, primed with 1.0 μg 17β-estradiol (E2) sc on days 3 and 4, injected with 500 μg progesterone (0.5 ml 30% ethanol in saline sc) on day 5, and decapitated (0830–0930 h) at various times thereafter. Progesterone injection resulted in the following significant changes: Rnaccumulation of 1 h and then retuRnto control levels by 9–72 h; and Re depletion at 1 h, partial increase by 9–12 h, and secondary decrease to a minimum at 24–72 h. Vehicle injection resulted in no changes in Rn(nor in Rc depletion at 1 h), but Rc was decreased 25% by 12 h to the level of Rc 12 h postprogesterone. Thereafter, Rc levels in the two injection groups were similar. Rc in uninjected rats remained significantly higher at 24 h than in either injection group. Adrenalectomized-ovariectomized rats (day 0, as above) showed significantly decreased Rc 24 h after progesterone (5.0 mg sc) injection but not after corticosterone or vehicle. Thus, in adrenal-intact rats, vehicle injection seems to result in adrenal steroid release (including progesterone) and subsequent chronic (i.e. no immediate translocation) effects on uterine Rc. In adrenal-intact rats, 500 μg or 5 mg progesterone (but not the vehicle alone) inhibited E2-induced uterine ballooning. The progesterone-induced depression of Rc at 24 h was overcome/inhibited by E2 injection 12 h postprogesterone, eliminating the possibility of an irreversible block in Rc synthesis. These data indicate that progesterone injection in the rat results in three phases of response by rat uterine progesterone receptors: 1) nuclear translocation, 2) a transient cytosol replenishment, and 3) apparent depression of Rc.