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Transplacental Toxicology Workgroup, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences Research Triangle Park, North Carolina 27709
Address requests for reprints to: Dr. Kenneth S. Korach, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709.
Abstract
Estrogen receptor levels were measured in uteri from ovariectomized-hypophysectomized mice. Cytosolic estrogen receptor levels had a range of 1.65–3.83 x 10–13 mol/100 µg DNA and varied significantly with time after surgery. Nuclear receptor levels also varied with time and had a range of 0.26–1.19 x 10–13 mol/100 µg DNA. Microsomal receptor levels varied from 0.24–0.72 x 10–13 mol/100 µg 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-adrerialectomized mouse uterus. The ability of the ovariectomized-hypophysectomized mouse uterus 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 similiar growth response to estrogen stimulation. The temporal pattern of estrogen receptor distribution was determined in uteri from ovariectomized-adrenalectomized mice; there were two 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 µg/ml, respectively. The differences in progesterone levels correlate with previously reported differences in uterine estrogen receptor levels. Thus, data from this system suggest that adrenal-derived progesterone may play a greater role in regulating estrogen receptor levels in target tissues than was previously thought. (Endocrinology 114: 108, 1984)
Received November 8, 1983.
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