CRH deficiency impairs but does not block pituitary-adrenal responses to diverse stressors
CRH deficiency impairs but does not block pituitary-adrenal responses to diverse stressors
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DOI：
10.1159/000054524
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发表时间：
2000-02-01
影响因子：
4.1
通讯作者：
Majzoub, JA
中科院分区：
文献类型：
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作者：
Jacobson, L;Muglia, LJ;Majzoub, JA
我们之前观察到促肾上腺皮质激素释放激素（CRH）缺乏（基因敲除，CRH KO）小鼠对束缚应激有显着的皮质酮反应，尽管有所下降。由于不同的压力源已被证明会影响不同的促垂体神经元群，因此我们使用低血糖和低血容量来测试是否由约束以外的刺激引起不依赖于 CRH 的垂体-肾上腺激活。禁食的 CRH KO 小鼠中注射胰岛素会引起皮质酮的增加，该增加明显低于野生型小鼠，但相对于相应的 KO 对照来说略有显着性。与肾上腺皮质功能受损一致，雌性 CRH KO 小鼠中低血糖诱导的肾上腺素分泌减少。 CRH KO 小鼠眼眶后出血引起的低血容量也显着升高皮质酮。与野生型小鼠中应激诱导的促肾上腺皮质激素 (ACTH) 显着增加相反，CRH KO 小鼠中的促肾上腺皮质激素 (ACTH) 增加是轻微的、短暂的，并且在不频繁采样的情况下很难检测到。野生型和 CRH KO 小鼠之间，约束诱导的白细胞介素 6 (IL-6) 水平相似，这反对因 CRH 缺陷而导致 IL-6 对约束的反应发生代偿性变化。 CRH输注增强了肾上腺皮质对约束的反应，与基础皮质酮水平的影响无关，这表明在应激期间除了CRH之外的因素也会增强垂体-肾上腺活性。我们的结论是，尽管应激诱导的垂体肾上腺活动不需要 CRH 的急剧增加，但需要 CRH 来支持应激期间肾上腺皮质轴对其他内分泌或神经因素的正常反应幅度。版权所有 (C) 2000 S. Karger AG，巴塞尔。
We have previously observed significant, albeit decreased, corticosterone responses to restraint stress in corticotropin releasing hormone (CRH)-deficient (knockout, CRH KO) mice. Because different stressors have been shown to engage different populations of hypophysiotropic neurons, we have used hypoglycemia and hypovolemia to test whether CRH-independent pituitary-adrenal activation is evoked by stimuli other than restraint. Insulin injection in fasted CRH KO mice elicited increases in corticosterone that were markedly lower than those in wild type but marginally significant relative to corresponding KO controls. Consistent with impaired adrenocortical function, hypoglycemia-induced epinephrine secretion was reduced in female CRH KO mice. Hypovolemia produced by retro-orbital bleeding also significantly elevated corticosterone in CRH KO mice. In contrast to significant stress-induced increases in corticotropin (ACTH) in wild-type mice, those in CRH KO mice were slight, transient and difficult to detect without frequent sampling. Restraint-induced interleukin-6 (IL-6) levels were similar between wild-type and CRH KO mice, arguing against compensatory changes in IL-6 responses to restraint due to CRH deficiency. CRH infusion enhanced adrenocortical responses to restraint independently of effects on basal corticosterone levels, suggesting that pituitary-adrenal activity is augmented by factors besides CRH during stress. We conclude that although stress-induced pituitary-adrenal activity does not require acute increases in CRH, CRH is required to support the normal amplitude of adrenocortical axis responsiveness to other endocrine or neural factors during stress. Copyright (C) 2000 S. Karger AG, Basel.