Glucocorticoid blockade reverses psychological stress-induced abnormalities in epidermal structure and function
Glucocorticoid blockade reverses psychological stress-induced abnormalities in epidermal structure and function
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DOI：
10.1152/ajpregu.00010.2006
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发表时间：
2006-12-01
影响因子：
2.8
通讯作者：
Feingold, Kenneth R.
中科院分区：
文献类型：
--
作者：
Choi, Eung-Ho;Demerjian, Marianne;Feingold, Kenneth R.
许多皮肤疾病的不利影响，心理应激（PS），但负责的机制知之甚少。最近的研究表明，PS降低表皮的增殖和分化，损害渗透屏障的稳态，并降低角质层的完整性。PS还增加了内源性糖皮质激素（GC）的产生，全身和局部GC对表皮结构和功能的不良影响与PS相似。因此，我们假设PS中内源性GC的增加介导了其不良的皮肤效应。为了验证这一假设，我们使用了两种独立的方法，给予RU-486，一种GC受体拮抗剂，抑制GC的作用，或antalarmin，一种促肾上腺皮质激素释放激素（CRH）受体拮抗剂，防止增加GC的生产，在面对PS。抑制GC的作用或产生可防止PS诱导的表皮细胞增殖和分化下降、渗透性屏障稳态受损和角质层（SC）完整性降低。此外，渗透性屏障稳态异常的病理生理学基础;即，板层体产生和分泌减少，通过抑制GC作用恢复正常。类似地，SC完整性降低的机制基础，即，角蛋白桥粒的减少也通过GC作用的抑制而正常化。因此，PS对表皮结构和功能的许多不良影响可归因于内源性GC增加，相反，减少GC产生或作用的方法可能有益于PS引起或加重的皮肤疾病。
Many cutaneous disorders are adversely affected by psychological stress (PS), but the responsible mechanisms are poorly understood. Recent studies have demonstrated that PS decreases epidermal proliferation and differentiation, impairs permeability barrier homeostasis, and decreases stratum corneum integrity. PS also increases the production of endogenous glucocorticoids (GC), and both systemic and topical GC cause adverse effects on epidermal structure and function similar to those observed with PS. We therefore hypothesized that increased endogenous GC in PS mediates its adverse cutaneous effects. To test this hypothesis, we used two independent approaches, administering either RU-486, a GC receptor antagonist that inhibits GC action, or antalarmin, a corticotropin-releasing hormone (CRH) receptor antagonist that prevents increased GC production in the face of PS. Inhibition of either GC action or production prevents the PS-induced decline in epidermal cell proliferation and differentiation, impairment in permeability barrier homeostasis, and decrease in stratum corneum (SC) integrity. Moreover, the pathophysiological basis for the abnormality in permeability barrier homeostasis; i.e., decreased lamellar body production and secretion, is restored toward normal by inhibition of GC action. Similarly, the mechanistic basis for the decrease in SC integrity, i.e., a reduction in corneodesmosomes, is also normalized by inhibition of GC action. Thus many of the adverse effects of PS on epidermal structure and function can be attributed to increased endogenous GC and conversely, approaches that either reduce GC production or action might benefit cutaneous disorders that are provoked or exacerbated by PS.