Estrogen Action in the Mouse Uterus: The Influence of the Neuroendocrine-Adrenal Axis

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Abstract
Estrogen receptor levels were measured in uteri from ovariectomized-hypophysectomized mice. Cytosolic estrogen receptor levels had a range of 1.65-3.83 .times. 10-13 mol/100 .mu.g DNA and varied significantly with time after surgery. Nuclear receptor levels also varied with time and had a range of 0.26-1.19 .times. 10-13 mol/100 .mu.g DNA. Microsomal receptor levels varied from 0.24-0.72 .times. 10-13 mol/100 .mu.g DNA. Concurrent temporal changes in uterine or vaginal epithelial histology were not observed. Binding properties of the estrogen receptor from the ovariectomized-hypophysectomized mouse uterus were determined; Scatchard analysis of saturation binding data showed one class of binding sites (Kd = 1.32 nM; n = 276 fmol/mg protein) with values similar to those obtained from ovariectomized-hypophysectomized mouse uterus. The ability of the ovariectomized-hypophysectomized mouse to respond to estrogen stimulation was determined in uterine wet weight and DNA synthesis assays; uteri from ovariectomized-hypophysectomized mice responded to estrogen in the same way as uteri from ovariectomized mice. Uteri from ovariectomized-adrenalectomized mice showed a similar growth response to estrogen stimulation. The temporal pattern of estrogen receptor distribution was determined in uteri from ovariectomized-adrenalectomized mice; there were 2 peaks of nuclear receptor translocation at 1 and 8 h, but the rate of cytosol receptor replenishment was slower than that previously seen in ovariectomized mouse uteri. Circulating estrogen and progesterone levels were measured in ovariectomized, ovariectomized-hypophysectomized and ovariectomized-adrenalectomized mice at different times after surgery. There was no significant difference in systemic estradiol levels among the groups. However, there were significant differences in progesterone levels; mean values from ovariectomized, ovariectomized-hypophysectomized and ovariectomized-adrenalectomized mice were 6.5, 2.1 and 0.029 ng/ml, respectively. The differences in progesterone levels correlate with previously reported differences in uterine estrogen receptor levels. Adrenal-derived progesterone may play a greater role in regulating estrogen receptor levels in target tissues than was previously thought.

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