CORTICOSTERONE RECEPTORS DECLINE IN A SITE-SPECIFIC MANNER IN THE AGED RAT-BRAIN
CORTICOSTERONE RECEPTORS DECLINE IN A SITE-SPECIFIC MANNER IN THE AGED RAT-BRAIN
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DOI：
10.1016/0006-8993(83)90024-0
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发表时间：
1983-01-01
期刊：
影响因子：
2.9
通讯作者：
MCEWEN, BS
中科院分区：
文献类型：
--
作者：
SAPOLSKY, RM;KREY, LC;MCEWEN, BS
在体内和体外测定了幼年和老年大鼠脑和脑下垂体中可能存在的糖皮质激素受体。给去肾上腺大鼠注射一定剂量的放射性标记皮质酮和未标记皮质酮，2 h后测定脑垂体和5个脑区精制核团中[3 H]皮质酮水平。在老年受试者中，海马体和杏仁体中皮质酮结合位点的最大数量显著减少；所有其他区域都没有表现出与年龄相关的变化。老龄大鼠脑内[~3H]地塞米松(DEX)的核摄取未见下降。由于地塞米松在体内选择性地与非神经性受体相互作用，糖皮质激素结合缺陷对神经元是选择性的。随后在体外评估胞浆制剂中糖皮质激素受体水平的研究显示，海马体和杏仁体中的糖皮质激素受体水平显着下降，数量上与观察到的这些基因位点的核结合下降相当。这表明，导致核耗竭的主要因素可能是胞质受体数量的减少，而不是其他可能的因素，如受体亲和力的降低或类固醇受体复合体的移位。这种下降可能对一些边缘功能起作用，这些功能受糖皮质激素的影响，并随着年龄的增长而出现缺陷。
Putative glucocorticoid receptors were measured in the brain and pituitary glands of young and aged rats in vivo and in vitro. Adrenalectomized rats were injected with a set dose of radiolabeled corticosterone plus unlabeled corticosterone; 2 h later [3H]corticosterone levels were measured in purified nuclear pellets from pituitary and 5 brain regions. Substantial decreases were seen in aged subjects in the maximal number of corticosterone binding sites in hippocampus and amygdala; all other regions showed no age-related changes. There were no declines in the nuclear uptake of [3H]dexamethasone (DEX) in the aged rat brains. Since DEX interacts selectively with non-neuronal receptors in vivo, the deficit in glucocorticoid binding is selective for neurons. Subsequent studies assessing glucocorticoid receptor levels in cytosol preparations in vitro revealed significant declines in hippocampus and amygdala quantitatively comparable to the decline observed in nuclear binding in these loci. This suggests that the primary deficit leading to nuclear depletion may be the reduction of cytosolic receptor number, rather than other possible factors such as the reduction in receptor affinity or translocation of steroid-receptor complex. This decline may play a role in a number of limbic functions which are influenced by glucocorticoids and show deficits with age.