Sapolsky R M, Krey L C, McEwen B S
Proc Natl Acad Sci U S A. 1984 Oct;81(19):6174-7. doi: 10.1073/pnas.81.19.6174.
The hippocampus is the principal target site in the brain for adrenocortical steroids, as it has the highest concentration of receptor sites for glucocorticoids. The aged rat has a specific deficit in hippocampal glucocorticoid receptors, owing in large part to a loss of corticoid-sensitive neurons. This deficit may be the cause for the failure of aged rats to terminate corticosterone secretion at the end of stress, because extensive lesion and electrical stimulation studies have shown that the hippocampus exerts an inhibitory influence over adrenocortical activity and participates in glucocorticoid feedback. We have studied whether it is the loss of hippocampal neurons or of hippocampal glucocorticoid receptors in the aged rat that contributes most to this syndrome of corticosterone hypersecretion. To do this, we used two model systems for producing reversible glucocorticoid receptor depletion in the hippocampus, and we found that depletion of receptors without inducing cell loss results in corticosterone hypersecretion. Furthermore, correction of the receptor deficit results in normalization of corticosterone secretion. These results focus attention on the hippocampus as an important glucocorticoid sensor in relation to the stress response. They also provide important new physiological correlates for the remarkable plasticity of the hippocampal glucocorticoid receptor system, which is under independent control by corticosterone and by vasopressin.
海马体是大脑中肾上腺皮质类固醇的主要靶位点，因为它拥有糖皮质激素受体位点的最高浓度。老年大鼠在海马体糖皮质激素受体方面存在特定缺陷，这在很大程度上归因于皮质激素敏感神经元的丧失。这种缺陷可能是老年大鼠在应激结束时无法终止皮质酮分泌的原因，因为广泛的损伤和电刺激研究表明，海马体对肾上腺皮质活动施加抑制性影响并参与糖皮质激素反馈。我们研究了在老年大鼠中，是海马体神经元的丧失还是海马体糖皮质激素受体的丧失对这种皮质酮分泌过多综合征的影响最大。为此，我们使用了两种模型系统来在海马体中产生可逆的糖皮质激素受体耗竭，并且我们发现受体耗竭而不诱导细胞损失会导致皮质酮分泌过多。此外，受体缺陷的纠正会导致皮质酮分泌正常化。这些结果将注意力集中在海马体作为与应激反应相关的重要糖皮质激素传感器上。它们还为海马体糖皮质激素受体系统的显著可塑性提供了重要的新生理关联，该系统受皮质酮和血管加压素的独立控制。
