Peiffer A, Lapointe B, Barden N
Laboratory of Molecular Psychogenetics, CHUL Research Centre, Ste-Foy, Quebec, Canada.
Endocrinology. 1991 Oct;129(4):2166-74. doi: 10.1210/endo-129-4-2166.
Differences in the regulation of type II glucocorticoid receptor (GR) mRNA levels in female rat brain regions involved in the control of the hypothalamic-pituitary-adrenal axis were studied by Northern blot analysis after chronic administration of corticosterone or dexamethasone to adrenalectomized (ADX), ovariectomized (OVX), and ADX/OVX animals. The effect of chronic estradiol or progesterone treatment of intact animals was also studied. Our results show that type II GR mRNA levels of ADX animals were significantly increased above control values in amygdala (140%) and hippocampus (196%), but not in hypothalamus. These increased transcript levels were down-regulated by corticosterone or dexamethasone, with the exception of those in the amygdala, where corticosterone had no effect. Ovariectomy significantly increased hypothalamic GR mRNA content (174%) over control values, and this increase was sensitive to dexamethasone. The combined effect of adrenalectomy/ovariectomy on GR mRNA levels was greater than that of adrenalectomy only in amygdala. Corticosterone increased amygdala transcript levels in OVX and ADX/OVX animals. Estradiol administration to intact animals raised the GR mRNA content of amygdala, while progesterone treatment had no effect on any of the brain regions studied. We conclude that there exists heterogeneity with respect to type II GR mRNA regulation by corticosterone and dexamethasone in brain regions of ADX female rats, and that certain limbic structures show greater sensitivity to these hormonal manipulations, suggesting a more prominent role in the regulation of the hypothalamic-pituitary-adrenal axis. Our results also suggest that circulating estrogens can influence the sensitivity of brain structures (i.e. hypothalamus and amygdala) to glucocorticoids by altering GR mRNA levels. These regions may represent integration sites at which gonadal steroids are able to alter stress hormone secretion.
通过对肾上腺切除（ADX）、卵巢切除（OVX）以及ADX/OVX的雌性大鼠长期给予皮质酮或地塞米松后，采用Northern印迹分析法研究了参与下丘脑 - 垂体 - 肾上腺轴调控的雌性大鼠脑区中II型糖皮质激素受体（GR）mRNA水平的调节差异。同时也研究了对完整动物长期给予雌二醇或孕酮的影响。我们的结果表明，ADX动物的杏仁核（140%）和海马体（196%）中II型GR mRNA水平显著高于对照值，但在下丘脑中未出现这种情况。除杏仁核中皮质酮无作用外，这些升高的转录水平被皮质酮或地塞米松下调。卵巢切除使下丘脑GR mRNA含量比对照值显著增加（174%），且这种增加对地塞米松敏感。肾上腺切除/卵巢切除对GR mRNA水平的联合作用仅在杏仁核中大于单纯肾上腺切除的作用。皮质酮增加了OVX和ADX/OVX动物杏仁核的转录水平。对完整动物给予雌二醇可提高杏仁核的GR mRNA含量，而孕酮处理对所研究的任何脑区均无影响。我们得出结论，ADX雌性大鼠脑区中皮质酮和地塞米松对II型GR mRNA的调节存在异质性，并且某些边缘结构对这些激素操作表现出更高的敏感性，表明其在调节下丘脑 - 垂体 - 肾上腺轴中发挥更突出的作用。我们的结果还表明，循环雌激素可通过改变GR mRNA水平影响脑结构（如下丘脑和杏仁核）对糖皮质激素的敏感性。这些区域可能代表性腺类固醇能够改变应激激素分泌的整合位点。
