Effects of estrogen and progesterone on cytoplasmic estrogen receptor and rates of protein synthesis in rat uterus

Changes in total cytoplasmic estrogen receptor (E₂-R_c) concentrations were compared to changes in rates of protein synthesis after steroid treatment in uterine tissue of long-term castrate Sprague Dawley rats. Animals were treated with estradiol 17β (E₂) alone or with progesterone (P₄) after 24 h of E₂ "priming". E₂-R_c concentration was "modulated" by E₂ (0.1 μg I.P.) in two distinct temporal phases: (A) Short term depletion with restoration to basal E₂-R_c/mg DNA occurred by 20 h after E₂ treatment. (B) Increases in E₂-R_c above basal levels were seen after 20-24 h. Twenty-four h after E₂ treatment, the administration of P₄ (1.0 mg s.c.) caused the elevated concentration of total E₂-R_c to decrease to base line levels within 2h. As determined from E₂-R_c decay experiments, modulation of E₂-R_c by E₂ or P₄ was not caused by activation of some soluble cytoplasmic receptor precursor nor by degradation (through proteolytic enzymes) of functional E₂-R_c. Uterine protein synthesis was monitored by pulse-labeling with [³⁵S]-methionine under the same treatment schedule as used for E₂-R_c quantitation. Both E₂ and P₄ stimulated incorporation of [³⁵S]-methionine into ribosomal, cytoplasmic and nuclear fractions. Increases in rates of [³⁵S]-methionine incorporation were interpreted as a demonstration of "hypertrophy". Since hypertrophy accompanied treatment with both estradiol and progesterone, and since differential modulation of E₂-R_c followed treatment with these steroids, the increase in E₂-R_c concentration following E₂ treatment appears to be a specific event which is distinct from hypertrophy. It is proposed that estrogen mediated increases in E₂R_c concentration represent a mechanism of molecular amplification which contributes in part to the cascading growth observed in the uterus. Conversely, progesterone antagonizes estrogen stimulation by depleting E₂-R_c concentration (in some unknown manner) thereby providing a biochemical "brake" to estrogen stimulation.