Tissue glucocorticoid resistance/hypersensitivity syndromes
Tissue glucocorticoid resistance/hypersensitivity syndromes
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DOI：
10.1016/s0960-0760(03)00218-8
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发表时间：
2003-06-01
影响因子：
4.1
通讯作者：
Chrousos, GR
中科院分区：
文献类型：
--
作者：
Kino, T;De Martino, MU;Chrousos, GR
糖皮质激素具有多种维持生命的功能，在许多疾病的治疗中发挥着重要作用。因此，组织对糖皮质激素敏感性的改变可能与许多病理状态的病程和治疗有关并影响其疗效。这种组织敏感性变化可能出现在最佳范围的任何一侧，分别为糖皮质激素抵抗或超敏反应，并且可能是全身性的或组织特异性的。由糖皮质激素受体（GR）基因失活突变引起的家族性/散发性糖皮质激素抵抗综合征是一种典型的单基因疾病，与先天性广泛性糖皮质激素不敏感有关，而一些自身免疫性、炎症性和过敏性疾病通常与炎症组织对糖皮质激素的抵抗有关。另一方面，糖皮质激素过敏已被认为与代谢综合征成分相关的内脏肥胖相关的胰岛素抵抗，以及由人类免疫缺陷病毒1型（HIV-1）感染引起的获得性免疫缺陷综合征（AIDS）有关。在此，我们回顾了5例家族性和3例散发性家族性/散发性糖皮质激素抵抗综合征的分子分析，并讨论了新发现的分子，如HIV-1辅助蛋白Vpr和Tat， flice相关巨蛋白（FLASH）和鸡卵白蛋白上游启动子转录因子II (COUP-TFII)，在GR活性的分子调控中的可能贡献。以及它们在病理条件下对糖皮质激素的组织敏感性变化的可能贡献。Elsevier Science Ltd.出版。
Glucocorticoids have a broad array of life-sustaining functions and play an important role in the therapy of many diseases. Thus, changes of tissue sensitivity to glucocorticoids may be associated with and influence the course and treatment of many pathologic states. Such tissue sensitivity changes may present on either side of an optimal range, respectively as glucocorticoid resistance or hypersensitivity, and may be generalized or tissue-specific. Familial/sporadic glucocorticoid resistance syndrome caused by inactivating mutations of the glucocorticoid receptor (GR) gene is a classic monogenic disorder associated with congenital, generalized glucocorticoid insensitivity, while several autoimmune, inflammatory and allergic diseases are often associated with resistance of the inflamed tissues to glucocorticoids. On the other hand, glucocorticoid hypersensitivity has been suggested in visceral obesity-related insulin resistance associated with components of the metabolic syndrome, and in the acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus type-1 (HIV-1) infection. Here, we have reviewed the molecular analyses of five familial and three sporadic cases of the familial/sporadic glucocorticoid resistance syndrome and discussed the possible contribution of newly identified molecules, such as HIV-1 accessory proteins Vpr and Tat, FLICE-associated huge protein (FLASH) and chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), on the molecular regulation of GR activity, as well as their possible contribution to changes in tissue sensitivity to glucocorticoids in pathologic conditions. Published by Elsevier Science Ltd.