Estrogen Action in the Mouse Uterus: Adrenal Modulation of Receptor Levels

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Abstract
Adrenal regulation of estradiol receptor levels was demonstrated in the ovariectomized mouse uterus. After ovariectomy, cytosol receptor levels initially followed a cyclic pattern, with a periodicity of approximately 5 days and a range of 2.25–4.80 × 10-13 mol estrogen receptor/100 μg DNA. Nuclear receptor levels showed marked fluctuations initially, but stabilized after day 15 at approximately 0.5 × 10-13 mol/100 μg DNA. Microsomal receptor levels also changed with time, but at a lower level than the cytosol and nuclear fluctuations. Concurrent cyclic changes in uterine or vaginal histology were not observed. After simultaneous ovariectomy and adrenalectomy, cytosol estradiol receptor levels remained low (≤1.5 × 10-13 mol/100 μg DNA) from 5–24 days, with no fluctuations. Nuclear and microsomal receptor levels changed, but to a smaller extent than those in ovariectomized mice. Concurrent histological changes were not observed. The residual cytosolic estrogen receptor remaining in the ovariectomized-adrenalectomized mouse uterus was characterized. Scatchard analysis of saturation binding data showed one class of binding sites with a Ka of 6.56 nM-1 (n = 350 fmol/ mg protein). This cytosol receptor sedimented at 8S on low salt sucrose density gradients. Receptor specificity was assessed by competitive equilibrium binding. The rank order of ligands was 17β-estradiol = diethylstilbestrol > nafoxidine. Progesterone and 5α-dihydrotestosterone showed no appreciable binding activity. After the injection of estradiol (10 μg/kg), 80–90% of the total available estrogen receptor translocated to the nuclear compartment. This translocated receptor could stimulate uterine hypertrophy and hyperplasia, as assessed in 1- and 3-day bioassays, and was able to initiate progesterone receptor synthesis. From these results, we conclude that the adrenal can modulate uterine estrogen receptor levels.