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Progesterone inhibition of estrogen receptor replenishment in ovine endometrium.

The influence of exogenous progesterone and estradiol on the concentration of total cytoplasmic and nuclear estrogen receptor in endometrium of ovariectomized ewes was studied and the effect of the respective steroid treatments on the receptor-mediated translocation of estrogen to the nucleus determined. 16 ovariectomized ewes were assigned to treatment groups as follows: Group 1 controls; Group 2 estradiol-17beta (EZ) implants (silastic capsules packed with 54 + or -3 mg); Group 3 progesterone (P) (15 mg twice daily); and Group 4 EZ + P. Control and P-treated animals were implanted with empty silastic capsules. Blood samples were collected on Days 0 and 2-7 for analysis for EZ and P. Ewes were sacrificed on Day 7 and the uteri were removed. Total specific nuclear and cytoplasmic estrogen binding sites were determined by use of tritiated estradiol exchange assay. Tritiated E2 bound to total cytoplasmic and nuclear receptors was greater (p less than .05) in endometirum of E2 treated ewes (10.4 + or -7.27 and .23 + or -.06 fmoles/mcg DNA respectively) than in endometrium of control P- and E2 + P-treated animals (1.62 + or -.26 and .13 + or -.02 fmoles/mcg DNA respectively). An average of 81 + or -1% of the tritiated E2 bound to available cytoplasmic receptors was translocated to the nucleus during incubation of endometrium of ewes from all treatment groups. The concentration of tritiated E2 specifically bound in the cytoplasm and translocated to the nucleus during incubation was greater in the endometrium of controls P-treated and E2 + P-treated groups. Concentrations of labeled E2 in the cytoplasm after in vitro translocation was greater in the endometrium of E2-treated ewes than in the endometrium of the other treatment groups. It is suggested that P antagonizes estrogen binding in the uterus by decreasing the concentration of cytoplasmic estrogen receptor.