The effects of ovarian hormones on stressor-induced hormonal responses, glucocorticoid receptor expression and translocation, and genes related to receptor signaling in adult female rats

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Abstract
Estradiol potentiates hypothalamic-pituitary-adrenal activity and delays the return of glucocorticoid secretion to baseline after a stressor exposure in female rats; we investigated whether estradiol effects involve actions on glucocorticoid receptor (GR) translocation and expression of receptor co-chaperones. In Experiment 1 intact females and ovariectomized (OVX) females were treated for four days with vehicle (VEH), 17β-estradiol benzoate (EB), or EB and progesterone (EB + P). Samples were taken from rats in the home cage (baseline) or after 30 min of restraint stress in a plastic restrainer (post-restraint) (n = 10/group). OVX-VEH treatment reduced baseline and post-restraint plasma concentrations of corticosterone versus all other treatments. Western blots indicated that OVX-VEH treated rats had greater hippocampal cytosolic GR expression than other treatments. Stress increased hippocampal nuclear GR expression, but without treatment differences. In Experiment 2 OVX rats were treated daily with VEH, EB, or EB + P (n = 8/group). OVX-VEH rats showed a lower stimulation of corticosterone secretion by restraint stress than other treatments and OVX-EB + P treated rats had lower concentrations than the OVX-EB group, suggesting progesterone mitigated estradiol effects. Quantitative polymerase chain reaction experiments indicated that stress increased Fkbp5 mRNA in the ventral hippocampus, with no effect of stress or treatment on Nr3c1 (GR), Nr3c2 (MR), Fkbp4, Bag1, or Ncoa1 (SRC-1) expression. Thus, the hypothesis is that estradiol effects on negative feedback are mediated by altered expression of receptor co-chaperones or co-modulators in the hippocampus was not supported. Estradiol may blunt feedback by limiting the availability of cytosolic GR protein.
Funding Information
  • Natural Sciences and Engineering Research Council of Canada (288348)
  • NSERC Alexander Graham Bell Canada Graduate Scholarship and an Ontario Graduate Scholarship
  • MLM holds an Ontario Trillium Scholarship

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