Eldridge J C, Fleenor D G, Kerr D S, Landfield P W
Department of Physiology and Pharmacology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27103.
Brain Res. 1989 Jan 30;478(2):248-56. doi: 10.1016/0006-8993(89)91505-9.
Several recent investigations have reported a decline of rat hippocampal corticosteroid-binding receptors (CSRs) with aging. This decline has been proposed to be an initial cause (through disinhibition) of the elevated adrenal steroid secretion that apparently occurs with aging; however, it could instead be an effect of corticoid elevation (through down-regulation). In order to assess the effects of age on CSR biosynthetic capacity in the absence of down-regulatory influences of endogenous corticoids, as well as to study aging changes in CSR plasticity, we examined the up-regulation of hippocampal CSR that follows adrenalectomy (ADX). The rat hippocampus contains at least two types of CSR binding and differential analysis of types I and II CSR was accomplished by selective displacement of [3H]corticosterone with RU-28362, a specific type II agonist. In young (3 months old) Fischer-344 rat hippocampus, up-regulation of type II binding above 2-day ADX baseline was present by 3-7 days and increased still further by 8-10 days post-ADX; type I CSR density did not change significantly between 1 and 10 days post-ADX. However, in aged (24-26 months old) rats, type II CSR up-regulation did not occur over the 10 day post-ADX period. Thus, the age-related impairment of type II up-regulation may reflect an intrinsic deficit in CSR biosynthesis or lability that is independent of the acute endogenous adrenal steroid environment.
最近的几项研究报告称，随着年龄增长，大鼠海马体中的皮质类固醇结合受体（CSR）数量会减少。有人认为这种减少是衰老过程中肾上腺类固醇分泌增加的初始原因（通过去抑制作用）；然而，它也可能是皮质类固醇升高的结果（通过下调作用）。为了评估在没有内源性皮质类固醇下调影响的情况下年龄对CSR生物合成能力的影响，以及研究CSR可塑性的衰老变化，我们检测了肾上腺切除术后（ADX）海马体CSR的上调情况。大鼠海马体至少含有两种类型的CSR结合，通过用特异性II型激动剂RU-28362选择性置换[3H]皮质酮，完成了I型和II型CSR的差异分析。在年轻（3个月大）的Fischer-344大鼠海马体中，II型结合在ADX后3-7天超过2天ADX基线水平出现上调，并在ADX后8-10天进一步增加；I型CSR密度在ADX后1至10天之间没有显著变化。然而，在老年（24-26个月大）大鼠中，II型CSR在ADX后10天内没有出现上调。因此，与年龄相关的II型上调受损可能反映了CSR生物合成或不稳定性的内在缺陷，这与急性内源性肾上腺类固醇环境无关。
