Sarabdjitsingh R Angela, Meijer Onno C, Schaaf Marcel J M, de Kloet E Ron
Division of Medical Pharmacology, Leiden/Amsterdam Centre for Drug Research/Leiden University Medical Centre, University of Leiden Einsteinweg 55, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Brain Res. 2009 Jan 16;1249:43-53. doi: 10.1016/j.brainres.2008.10.048. Epub 2008 Oct 31.
Corticosteroids exert important effects on brain function via glucocorticoid (GRs) and mineralocorticoid receptors (MRs) by inducing receptor translocation to the nucleus, where the receptor-ligand complexes modulate transcription of target genes. Based on studies describing uneven receptor expression patterns, regionally different corticosterone effects, and the importance of timing of corticosteroid effects, we hypothesized that differential patterns of MR and GR translocation exist in the rat hippocampus in response to a single glucocorticoid stimulus. Temporal patterns of receptor translocation were investigated in both intact and adrenalectomised (ADX) male Sprague-Dawley rats. Animals were sacrificed at different time points after intraperitoneal administration of 3 mg/kg corticosterone. Specific MR and GR primary antibodies were used for immunohistochemistry and confocal microscopy to visualize and quantify receptor subcellular localisation in the different subregions of the hippocampus. Results indicate (1) significant subregion-specific differences in translocation patterns for both MR and GR, with respect to the extent and timing of nuclear translocation and (2) specific differences between ADX and intact animals that are most prominent in the dentate gyrus: while corticosterone given to intact animals induced a marked nuclear increase in both MR and GR, in ADX animals nuclear MR signal was already elevated in the absence of hormone, and did not change after steroid treatment. We conclude that in response to a single stress-like increase in corticosterone distinct region-specific MR- and GR-dependent translocation patterns exist in the rat hippocampus, which may underlie region-specific effects relevant to homeostatic control.
皮质类固醇通过糖皮质激素受体（GRs）和盐皮质激素受体（MRs）对脑功能发挥重要作用，其机制是诱导受体易位至细胞核，在细胞核中受体 - 配体复合物调节靶基因的转录。基于描述受体表达模式不均一、皮质酮效应存在区域差异以及皮质类固醇效应时机重要性的研究，我们推测在大鼠海马体中，对单一糖皮质激素刺激的反应存在MR和GR易位的差异模式。在完整和肾上腺切除（ADX）的雄性Sprague - Dawley大鼠中研究了受体易位的时间模式。腹腔注射3 mg/kg皮质酮后，在不同时间点处死动物。使用特异性MR和GR一抗进行免疫组织化学和共聚焦显微镜检查，以可视化和量化海马体不同亚区域中受体的亚细胞定位。结果表明：（1）MR和GR的易位模式在亚区域特异性上存在显著差异，涉及核易位的程度和时间；（2）ADX动物和完整动物之间存在特定差异，在齿状回中最为明显：给完整动物注射皮质酮会导致MR和GR的核内显著增加，而在ADX动物中，在没有激素的情况下核MR信号已经升高，类固醇处理后没有变化。我们得出结论，在对皮质酮单次类似应激的增加反应中，大鼠海马体中存在不同的区域特异性MR和GR依赖性易位模式，这可能是与稳态控制相关的区域特异性效应的基础。
