The function of the HPA axis is subject to regulation by many factors, which achieve relevance under normal and pathological conditions. In the case of aging, this period of life is associated with disturbances of the HPA axis and signs of hippocampal vulnerability. We examined 20-month-old male rats, in which abnormalities of the HPA axis included altered response to stress, reduced effectiveness of the steroid negative feedback and low expression of hippocampal glucocorticoid receptors (GR). Estrogen treatment of aging rats normalized the response to stress, restored the dexamethasone inhibition of the stress response and increased GR density in defined hippocampal areas. Although estrogens could influence the hippocampus of aging animals directly, their effects could be also mediated by estrogen-sensitive forebrain cholinergic neurons projecting to the hippocampus. Additionally, estrogens normalized the deficient granule cell proliferation that aging mice present in the dentate gyrus, and attenuated several markers of hippocampal aging, such as astrocytosis, high lipofucsin content and neuronal loss in the hilus of the dentate gyrus. These effects may be important for the regulation of the HPA axis, in the context that hippocampal function as a whole was normalized by estrogen action. Therefore, estrogens are powerful neuroprotectants in cases of hippocampal dysfunction, and as part of this effect, they contribute to stabilize the function of the HPA axis.

译文

:HPA轴的功能受许多因素的调节,这些因素在正常和病理情况下均具有相关性。在衰老的情况下,这一时期与HPA轴的紊乱和海马体征相关。我们检查了20个月大的雄性大鼠,其中HPA轴异常包括对压力的反应改变,类固醇负反馈的有效性降低以及海马糖皮质激素受体(GR)的低表达。衰老大鼠的雌激素治疗使对压力的反应正常化,恢复了地塞米松对压力反应的抑制作用,并在限定的海马区增加了GR密度。尽管雌激素可以直接影响衰老动物的海马体,但它们的作用也可以由对海马体的雌激素敏感的前脑胆碱能神经元介导。另外,雌激素使衰老小鼠在齿状回中存在的缺乏的颗粒细胞增殖正常化,并减弱了海马衰老的几种标志物,例如星形细胞增多症,高脂褐素含量和齿状回中的神经元丢失。在通过雌激素作用使海马整体功能正常化的情况下,这些作用对于调节HPA轴可能很重要。因此,在海马功能障碍的情况下,雌激素是强大的神经保护剂,作为这种作用的一部分,它们有助于稳定HPA轴的功能。

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