Negative regulation of corticotropin releasing factor expression and limitation of stress response
Negative regulation of corticotropin releasing factor expression and limitation of stress response
复制标题
DOI：
10.1080/10253890701391192
复制
发表时间：
2007-01-01
影响因子：
2.3
通讯作者：
Kamitakahara, Anna
中科院分区：
文献类型：
--
作者：
Aguilera, Greti;Kiss, Alexander;Kamitakahara, Anna
促肾上腺皮质激素释放因子(CRF)协调行为、自主神经和荷尔蒙对应激的反应。下丘脑-垂体-肾上腺(HPA)轴在CRF的刺激下激活，加压素(VP)从下丘脑小细胞神经元释放，从而从垂体前叶分泌ACTH，从肾上腺皮质分泌糖皮质激素，是应激的主要内分泌反应。目前的证据表明，在急慢性条件下，促肾上腺皮质激素分泌的主要调节因子是CRF，尽管在HPA轴的长时间激活过程中观察到小细胞VP和垂体VP V1b受体表达的选择性增加，这表明VP成为主要的调节因子。CRF释放后，需要激活CRF转录以恢复mRNA和多肽水平，但终止这一反应对于防止CRF和糖皮质激素产生慢性升高相关的病理至关重要。虽然糖皮质激素反馈在调节CRF的表达中起着重要作用，但糖皮质激素直接转录抑制CRF基因在整个反馈机制中的相对重要性尚不清楚。除了糖皮质激素外，CRF神经元中的细胞内反馈机制，包括诱导抑制形式的cAMP反应元件调节剂(CREM)，通过与正调控因子磷酸化CREB竞争来限制CRF的转录反应。在应激诱导激活后，CRF转录的快速抑制可能有助于限制应激反应，并有助于防止与过度产生CRF相关的疾病。
Corticotropin releasing factor (CRF) coordinates behavioral, autonomic and hormonal responses to stress. Activation of the hypothalamic pituitary adrenal (HPA) axis with stimulation of CRF and vasopressin (VP) release from hypothalamic parvocellular neurons, and consequent secretion of ACTH from the anterior pituitary and glucocorticoid from the adrenal cortex, is the major endocrine response to stress. Current evidence indicates that the main regulator of ACTH secretion in acute and chronic conditions is CRF, in spite of the fact that the selective increases in expression of parvocellular VP and pituitary VP V1b receptors observed during prolonged activation of the HPA axis have suggested that VP becomes the predominant regulator. Following CRF release, activation of CRF transcription is required to restore mRNA and peptide levels, but termination of the response is essential to prevent pathology associated with chronic elevation of CRF and glucocorticoid production. While glucocorticoid feedback plays an important role in regulating CRF expression, the relative importance of direct transcriptional repression of the CRF gene by glucocorticoids in the overall feedback mechanism is not clear. In addition to glucocorticoids, intracellular feedback mechanisms in the CRF neuron, involving induction of repressor forms of cAMP response element modulator (CREM) limit CRF transcriptional responses by competing with the positive regulator, phospho-CREB. Rapid repression of CRF transcription following stress-induced activation is likely to contribute to limiting the stress response and to preventing disorders associated with excessive CRF production.