Neurotransmitter regulation of the hypothalamic corticotropin-releasing hormone neuron
Neurotransmitter regulation of the hypothalamic corticotropin-releasing hormone neuron
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DOI：
10.1111/j.1749-6632.1995.tb44668.x
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发表时间：
1995-01-01
期刊：
影响因子：
2.3
通讯作者：
Calogero, AE
中科院分区：
文献类型：
--
作者：
Calogero, AE
促肾上腺皮质激素释放激素(CRH)是一种由41个氨基酸组成的多肽，是垂体ACTH释放的主要促分泌剂之一，主要由位于下丘脑室旁核(PVN)2的小细胞部的神经元合成，投射到正中隆起3，在那里CRH被释放到垂体门静脉血(HPB)。大量实验证据表明，脑室注射促肾上腺皮质激素释放激素(CRH)不仅参与调节ACTH的释放，而且能够复制应激时观察到的许多生理和行为反应。这些发现导致假设，这种神经肽可能是一个重要的整合因子，能够协调内分泌，自主神经和行为反应。PVN的4‘~CRH神经元从下丘脑和下丘脑外的许多脑区接受丰富的神经支配，认知刺激通过这些区域调节下丘脑-垂体-肾上腺(HPA)轴的活动。关于CRH释放的神经递质调节的大量文献产生了相互矛盾且往往不清楚的结论。诸如使用相对非特异性的药理学探针、不同给药途径的应用、麻醉的混淆效果和/或使用CRH分泌(ACTH和糖皮质激素)的间接评估等因素可能导致了相互矛盾的结果。此外，在对绵羊下丘脑CRH进行化学鉴定之前，对CRH分泌的量化依赖于测量移植下丘脑孵育液中ACTH释放特性的生物测定。考虑到下丘脑控制ACTH释放的多因素性质，用这些方法很难推断CRH的释放。6本文综述了乙酰胆碱(ACh)、儿茶酚胺(CAS)、组胺(HA)和5-羟色胺(SHT)对下丘脑CRH释放的影响，以及GABAhenzodiazepine(BZD)系统对抑制输入的影响。在简要概述神经解剖学底物之后，每一节都提供了这些神经递质在CRH释放中所起作用的一些最直接的证据。
Corticotropin-releasing hormone (CRH), a 41-amino-acid peptide, is one of the major secretagogues of pituitary ACTH release.'It is synthesized by neurons located mainly in the parvocellular division of the hypothalamic paraventricular nucleus (PVN) 2 that project to the median eminence3 where CRH is released into the hypophysial-portal blood (HPB). A large body of experimental evidence suggests that CRH, administered intracerebroventricularly (icv), is not only involved in the regulation of ACTH release, but is also capable of reproducing many of the physiologic and behavioral responses observed during stress. These findings led to the hypothesis that this neuropeptide may be an important integrative factor capable of coordinating endocrine, autonomic, and behavioral responses to~ tress. 4'~ CRH neurons of the PVN receive a copious innervation from many hypothalamic and extrahypothalamic brain regions through which cognitive stimuli modulate the activity of the hypothalamic-pituitary-adrenal (HPA) axis. The voluminous literature regarding the neurotransmitter regulation of CRH release has yielded conflicting and often unclear conclusions. Factors such as the use of relatively nonspecific phannacologic probes, application of varying routes of drug administration, the confounding effects of anesthesia, and/or the use of indirect assessments of CRH secretion (ACTH and glucocorticoids) may have contributed to the conflicting results. Moreover, before the chemical identification of CRH from sheep hypothalami,'quantization of CRH secretion relied on bioassays measuring the ACTH-releasing properties of the incubation medium of explanted hypothalami. With such methods, it is difficult to make inferences about CRH release given the multifactorial nature of hypothalamic control of ACTH release. 6 This paper reviews the effects of acetylcholine (ACh), catecholamines (CAs), histamine (HA), and serotonin (SHT), which are generally thought to stimulate hypothalamic CRH release, and the effects of the GABAhenzodiazepine (BZD) system, which mediates inhibitory inputs. Following a brief summary of the neuroanatomical substrate, each section presents some of the most direct evidence of the role played by these neurotransmitters on CRH release.