Green Matthew R, Marcolin Marina L, McCormick Cheryl M
a Psychology Department , Brock University , St Catharines , Canada.
b Biological Sciences Department , Brock University , St Catharines , Canada.
Stress. 2018 Mar;21(2):90-100. doi: 10.1080/10253890.2017.1409719. Epub 2017 Nov 30.
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.
雌二醇可增强雌性大鼠下丘脑 - 垂体 - 肾上腺的活性，并在应激源暴露后延迟糖皮质激素分泌恢复至基线水平；我们研究了雌二醇的作用是否涉及对糖皮质激素受体（GR）易位及受体共伴侣蛋白表达的影响。在实验1中，对完整雌性大鼠和去卵巢（OVX）雌性大鼠用溶剂（VEH）、17β - 雌二醇苯甲酸酯（EB）或EB与孕酮（EB + P）处理四天。在大鼠处于饲养笼中（基线）或在塑料束缚器中束缚应激30分钟后（束缚后）采集样本（每组n = 10）。与所有其他处理相比，OVX - VEH处理降低了基线和束缚后血浆皮质酮浓度。蛋白质免疫印迹表明，OVX - VEH处理的大鼠海马胞质GR表达高于其他处理。应激增加了海马核GR表达，但无处理差异。在实验2中，对OVX大鼠每日用VEH、EB或EB + P处理（每组n = 8）。OVX - VEH大鼠束缚应激刺激皮质酮分泌的程度低于其他处理，且OVX - EB + P处理的大鼠浓度低于OVX - EB组，提示孕酮减轻了雌二醇的作用。定量聚合酶链反应实验表明，应激增加了腹侧海马中Fkbp5 mRNA水平，应激或处理对Nr3c1（GR）、Nr3c2（MR）、Fkbp4、Bag1或Ncoa1（SRC - 1）表达无影响。因此，雌二醇对负反馈的影响是由海马中受体共伴侣蛋白或共调节因子表达改变介导的这一假设未得到支持。雌二醇可能通过限制胞质GR蛋白的可用性来减弱反馈。
