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

• Published in: Journal of steroid biochemistry Vol. 8; no. 3; pp. 205 - 212
• Main Authors: CouLson, P.B., Pavlik, E.J.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.03.1977
• Subjects: Animals; Castration; Estradiol - pharmacology; Female; Kinetics; Muscle Proteins - biosynthesis; Progesterone - pharmacology; Protein Biosynthesis - drug effects; Rats; Receptors, Estrogen - drug effects; Regression Analysis; Uterus - drug effects; Uterus - metabolism
• ISSN: 0022-4731
• DOI: 10.1016/0022-4731(77)90052-8

Changes in total cytoplasmic estrogen receptor (E 2-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 (E 2) alone or with progesterone (P 4) after 24 h of E 2 “priming”. E 2-R c concentration was “modulated” by E 2 (0.1 μg I.P.) in two distinct temporal phases: (A) Short term depletion with restoration to basal E 2-R c/mg DNA occurred by 20 h after E 2 treatment. (B) Increases in E 2-R c above basal levels were seen after 20–24 h. Twenty-four h after E 2 treatment, the administration of P 4 (1.0 mg s.c.) caused the elevated concentration of total E 2-R c to decrease to base line levels within 2h. As determined from E 2-R c decay experiments, modulation of E 2-R c by E 2 or P 4 was not caused by activation of some soluble cytoplasmic receptor precursor nor by degradation (through proteolytic enzymes) of functional E 2-R c. Uterine protein synthesis was monitored by pulse-labeling with [ 35S]-methionine under the same treatment schedule as used for E 2-R c quantitation. Both E 2 and P 4 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 E 2-R c followed treatment with these steroids, the increase in E 2-R c concentration following E 2 treatment appears to be a specific event which is distinct from hypertrophy. It is proposed that estrogen mediated increases in E 2R 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 E 2-R c concentration (in some unknown manner) thereby providing a biochemical “brake” to estrogen stimulation.