Modulation of estrogen receptors in four different target tissues: Differential effects of estrogen vs progesterone

The effect of pretreatment with estradiol-17β with or without progesterone on estradiol cytosolie receptors was investigated in 4 different target tissues from long term castrate Sprague-Dawley rats. Receptor assay was performed by hydroxylapatite adsorption and Scatchard analysis. Treatment with estradiol (0.1 μg/rat) for 48 h in vivo increased absolute cytosolic receptor concentrations per mg DNA 3-5-fold for uterine and vaginal tissue, but no increase was observed in pituitary or hypothalamic tissue. These increases in estradiol receptor concentration after 48 h of estrogen exposure should be distinguished from "replenishment" phenomenon after shorter time periods (15-20 h) which demonstrate recovery to baseline of "available" estrogen receptors. The increase in cytosolic estrogen receptors in uterine and vaginal tissue in response to estrogen is opposed by in vivo treatment with estrogen plus progesterone. This opposition cannot be explained by competition from progesterone or negative cooperative interaction with progesterone when analyzed by Scatchard plots and Hill coefficients. Deviations from linearity in Scatchard plots are not explainable in terms of positive or negative cooperativity between estrogen and progesterone. Neither estrogen stimulation of E₂-R₀ nor its opposition by P₄ were observed in pituitary or hypothalamic target tissues. These results support the concept of a single, non-interacting binding site for estrogen on the estrogen receptor with similar K_a values for E₂-R₀ in all four target tissues studied. However. the uterine and vagina "response" to E₂ stimulation, as measured by changes in E₂-R₀ binding sites. was statistically different from the response of pituitary or hypothalamic target tissue.