Estrogen action in the mouse uterus: the influence of the neuroendocrine-adrenal axis.
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 micrograms 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 micrograms DNA. Microsomal receptor levels varied from 0.24-0.72 X 10(-13) mol/100 micrograms 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-adrenalectomized 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 similar 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 ng/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.
D000311:Adrenal Glands / Q000502:physiology; D000315:Adrenalectomy; D000818:Animals; D002369:Castration; D003600:Cytosol / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D007016:Hypophysectomy; D007700:Kinetics; D051379:Mice; D008813:Mice, Inbred ICR; D011960:Receptors, Estrogen / Q000378:metabolism*; D014599:Uterus / Q000187:drug effects / Q000502:physiology*
D011960:Receptors, Estrogen; D004958:Estradiol