Jacobson L, Muglia L J, Weninger S C, Pacák K, Majzoub J A
Division of Endocrinology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Neuroendocrinology. 2000 Feb;71(2):79-87. doi: 10.1159/000054524.
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.
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）小鼠对束缚应激的皮质酮反应显著，尽管有所降低。由于已表明不同的应激源会激活不同群体的促垂体神经元，我们利用低血糖和低血容量来测试除束缚之外的刺激是否会引发不依赖CRH的垂体-肾上腺激活。对禁食的CRH KO小鼠注射胰岛素后，皮质酮水平升高，但其升高幅度明显低于野生型小鼠，不过相对于相应的KO对照小鼠仍有微弱的显著性差异。与肾上腺皮质功能受损一致，雌性CRH KO小鼠低血糖诱导的肾上腺素分泌减少。眼眶后出血导致的低血容量也使CRH KO小鼠的皮质酮显著升高。与野生型小鼠在应激时促肾上腺皮质激素（ACTH）显著增加相反，CRH KO小鼠的ACTH增加轻微、短暂，且不频繁采样很难检测到。野生型和CRH KO小鼠束缚诱导的白细胞介素-6（IL-6）水平相似，这表明不存在因CRH缺乏而导致的对束缚的IL-6反应的代偿性变化。CRH输注增强了对束缚的肾上腺皮质反应，且与对基础皮质酮水平的影响无关，这表明应激期间除CRH外其他因素也会增强垂体-肾上腺活性。我们得出结论，虽然应激诱导的垂体-肾上腺活性不需要CRH急性增加，但应激期间CRH是维持肾上腺皮质轴对其他内分泌或神经因素正常反应幅度所必需的。
