Taymans S E, DeVries A C, DeVries M B, Nelson R J, Friedman T C, Castro M, Detera-Wadleigh S, Carter C S, Chrousos G P
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Gen Comp Endocrinol. 1997 Apr;106(1):48-61. doi: 10.1006/gcen.1996.6849.
Basal plasma corticosterone levels in prairie voles (Microtus ochrogaster) are extremely high, in the absence of any apparent negative consequences of glucocorticoid excess. We tested the hypothesis that prairie voles are a novel rodent model of target tissue resistance to glucocorticoids. Prairie voles had a significantly higher adrenal-to-body weight ratio, 5- to 10-fold greater basal plasma corticosterone, and 2- to 3-fold greater basal plasma ACTH concentrations than montane voles (Microtus montanus) and rats. While plasma corticosterone binding globulin (CBG) was 2-fold higher in prairie voles than in rats, both estimated and directly measured plasma free corticosterone were significantly higher in prairie voles than in rats. Plasma corticosterone levels in prairie voles were responsive to both circadian cues and a stressor, but were resistant to suppression by the synthetic glucocorticoid, dexamethasone (DEX). Western blots of brain and liver protein extracts, using a glucocorticoid receptor (GR) antibody, revealed the presence of a approximately 97 kDa immunoreactive band, the expected size for GR. Binding assays revealed significantly lower DEX affinity of corticosteroid receptors (CR) in cytosol of prairie vole brain and liver than that in the same tissues in rats. We conclude that prairie voles are a novel rodent model of glucocorticoid resistance, and that decreased affinity of CR for ligand might be partially responsible for this phenomenon.
草原田鼠（Microtus ochrogaster）的基础血浆皮质酮水平极高，却没有任何明显的糖皮质激素过量的负面后果。我们检验了这样一个假设，即草原田鼠是一种对糖皮质激素具有靶组织抗性的新型啮齿动物模型。与山地田鼠（Microtus montanus）和大鼠相比，草原田鼠的肾上腺与体重之比显著更高，基础血浆皮质酮水平高5至10倍，基础血浆促肾上腺皮质激素（ACTH）浓度高2至3倍。虽然草原田鼠的血浆皮质酮结合球蛋白（CBG）比大鼠高2倍，但无论是估算的还是直接测量的血浆游离皮质酮，草原田鼠都显著高于大鼠。草原田鼠的血浆皮质酮水平对昼夜节律线索和应激源都有反应，但对合成糖皮质激素地塞米松（DEX）的抑制具有抗性。使用糖皮质激素受体（GR）抗体对脑和肝蛋白提取物进行的蛋白质免疫印迹分析显示，存在一条约97 kDa的免疫反应带，这是GR的预期大小。结合试验表明，草原田鼠脑和肝胞质溶胶中皮质类固醇受体（CR）的DEX亲和力显著低于大鼠相同组织中的DEX亲和力。我们得出结论，草原田鼠是一种新型的糖皮质激素抗性啮齿动物模型，CR对配体亲和力的降低可能部分导致了这一现象。
