Reul J M, Sutanto W, van Eekelen J A, Rothuizen J, de Kloet E R
Rudolf Magnus Institute, Utrecht, The Netherlands.
Adv Exp Med Biol. 1990;274:243-56. doi: 10.1007/978-1-4684-5799-5_15.
Corticosteroids interact with receptors in the central nervous system. These receptors display heterogeneity and can be distinguished as corticosterone- and aldosterone-binding mineralocorticoid receptors and dexamethasone-binding glucocorticoid receptors. Ligand specificity of mineralocorticoid receptors for either corticosterone or aldosterone seems to be determined by co-localized transcortin and the enzyme, 11 beta-hydroxysteroid dehydrogenase. Aldosterone-selective mineralocorticoid receptors appear to be present in the circumventricular organs and the AV3V region of the hypothalamus and mediate behavior that is driven by salt appetite. Highest concentrations of mineralocorticoid receptors are found in neurons of the hippocampus. These limbic mineralocorticoid receptor sites mediate tonic influences of corticosterone on brain processes. Glucocorticoid receptors bind corticosterone with a tenfold lower affinity than do mineralocorticoid receptors, and are widely distributed in neuronal and glial cells of the brain. Glucocorticoid receptors are involved in the termination of the stress response (negative feedback). Studies involving measurement of glucocorticoid receptor mRNA and binding sites have revealed that glucocorticoid receptors are subject to autoregulation. After ADX, glucocorticoid receptor concentration increases, but is reduced after chronic stress, chronic administration of glucocorticoids, and at senescence. A diminished glucocorticoid receptor concentration may compromise the negative feedback action exerted by glucocorticoids after stress. After ADX, mineralocorticoid receptor binding is acutely up-regulated and reaches its maximum between 7 and 24 hours post-ADX. Mineralocorticoid receptor mRNA level shows a transient increase following ADX. Long-term ADX has no effect on the mineralocorticoid receptor concentration, but, interestingly, chronic dexamethasone treatment results in an up-regulation of mineralocorticoid receptors. Mineralocorticoid receptor level is decreased at senescence, but this age-related decrement can be reversed by chronic treatment with the ACTH4-9 analog, ORG 2766. Functionally, mineralocorticoid receptors and glucocorticoid receptors are involved in different aspects of the organization of the stress response, and in conjunction they control the stress responsiveness of the animal.
皮质类固醇与中枢神经系统中的受体相互作用。这些受体具有异质性，可分为结合皮质酮和醛固酮的盐皮质激素受体以及结合地塞米松的糖皮质激素受体。盐皮质激素受体对皮质酮或醛固酮的配体特异性似乎由共定位的皮质素结合球蛋白和11β-羟基类固醇脱氢酶决定。醛固酮选择性盐皮质激素受体似乎存在于室周器官和下丘脑的AV3V区域，并介导由盐食欲驱动的行为。盐皮质激素受体的最高浓度见于海马神经元。这些边缘盐皮质激素受体位点介导皮质酮对脑过程的紧张性影响。糖皮质激素受体结合皮质酮的亲和力比盐皮质激素受体低10倍，广泛分布于脑的神经元和神经胶质细胞中。糖皮质激素受体参与应激反应的终止（负反馈）。涉及测量糖皮质激素受体mRNA和结合位点的研究表明，糖皮质激素受体受到自身调节。去肾上腺后，糖皮质激素受体浓度增加，但在慢性应激、长期给予糖皮质激素以及衰老时降低。糖皮质激素受体浓度降低可能会损害应激后糖皮质激素发挥的负反馈作用。去肾上腺后，盐皮质激素受体结合迅速上调，并在去肾上腺后7至24小时达到最大值。盐皮质激素受体mRNA水平在去肾上腺后短暂升高。长期去肾上腺对盐皮质激素受体浓度没有影响，但有趣的是，长期地塞米松治疗会导致盐皮质激素受体上调。盐皮质激素受体水平在衰老时降低，但这种与年龄相关的降低可通过促肾上腺皮质激素4-9类似物ORG 2766的长期治疗得到逆转。在功能上，盐皮质激素受体和糖皮质激素受体参与应激反应组织的不同方面，它们共同控制动物的应激反应性。
