Corticotropin-releasing hormone links pituitary adrenocorticotropin gene expression and release during adrenal insufficiency
Corticotropin-releasing hormone links pituitary adrenocorticotropin gene expression and release during adrenal insufficiency
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DOI：
10.1172/jci5250
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发表时间：
2000-05-01
影响因子：
15.9
通讯作者：
Majzoub, JA
中科院分区：
文献类型：
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作者：
Muglia, LJ;Jacobson, L;Majzoub, JA
促肾上腺皮质激素释放激素 (CRH) 缺陷 (KO) 小鼠提供了一个独特的系统来定义 CRH 在调节下丘脑 - 垂体 - 肾上腺 (HPA) 轴中的作用。尽管有多种慢性糖皮质激素不足的表现，但 CRH KO 小鼠的基础垂体阿黑皮质素原 (POMC) mRNA、垂体内促肾上腺皮质激素 (ACTH) 肽含量和血浆 ACTH 浓度并未升高。 KO 小鼠中正常的 POMC mRNA 含量取决于残留的糖皮质激素分泌，因为肾上腺切除后 KO 和 WT 小鼠的 POMC mRNA 含量都会增加；这种增加可以通过糖皮质激素替代来逆转，但不能通过醛固酮替代来逆转。然而，CRH KO 小鼠中 ACTH 的正常血浆水平并不依赖于残留量。糖皮质激素分泌，因为在肾上腺切除术后，尽管 POMC mRNA 含量增加，但这些水平并未经历 KO 小鼠中所见的正常增加。在肾上腺切除的 CRH KO 小鼠中，给予 CRH 可将 ACTH 分泌恢复至预期的高水平。因此，在肾上腺功能不全的情况下，糖皮质激素反馈本身的丧失会增加垂体中 POMC 基因的表达；但是CRH作用对于导致ACTH分泌增加是必要的。这可以解释为什么在停止长期糖皮质激素治疗后，CRH分泌的重新激活是从HPA轴的抑制中恢复的必要先决条件。
Corticotropin-releasing hormone (CRH)-deficient (KO) mice provide a unique system to define the role of CRH in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Despite several manifestations of chronic glucocorticoid insufficiency, basal pituitary proopiomelanocortin (POMC) mRNA, adrenocorticotrophic hormone (ACTH) peptide content within the pituitary, and plasma ACTH concentrations are not elevated in CRH KO mice. The normal POMC mRNA content in KO mice is dependent upon residual glucocorticoid secretion, as it increases in both KO and WT mice after adrenalectomy; this increase is reversed by glucocorticoid, but not aldosterone, replacement. However, the normal plasma levels of ACTH in CRH KO mice are not dependent upon residual. glucocorticoid secretion, because, after adrenalectomy, these levels do not undergo the normal increase seen in KO mice despite the increase in POMC mRNA content. Administration of CRH restores ACTH secretion to its expected high level in adrenalectomized CRH KO mice. Thus, in adrenal insufficiency, loss of glucocorticoid feedback by itself can increase POMC gene expression in the pituitary; but CRH action is essential for this to result in increased secretion ofACTH, This may explain why, after withdrawal of chronic glucocorticoid treatment, reactivation of CRH secretion is a necessary prerequisite for recovery from suppression of the HPA axis.