Scott L V, Dinan T G
Department of Psychiatry, Trinity College Medical School, St. James' Hospital, Dublin, Ireland.
Life Sci. 1998;62(22):1985-98. doi: 10.1016/s0024-3205(98)00027-7.
The role of arginine vasopressin (AVPNP) in the control of adrenocorticotropic hormone (ACTH) secretion is explored, and in particular, its involvement in various stress response paradigms which may be of relevance in our understanding of the pathophysiology of depression. VP is released from two sites in the hypothalamus; the parvicellular division of the paraventricular nucleus (PVN), where corticotropin releasing hormone (CRH) is also formed, and from the magnocellular neurons of the supraoptic nucleus (SON) and the PVN. The intricate interaction with CRH, the other main ACTH secretagogue, and with glucocorticoids, the inhibitory feedback component of hypothalamic-pituitary-adrenal-axis (HPA) activity, is outlined. That VP plays an important role in the stress response is now beyond doubt. Examination of the impact of psychological stressors on the differential expression of VP and CRH at a hypothalamic and pituitary level has been facilitated by advances in molecular biological techniques. Of importance has been the cloning of the V1b receptor gene, the receptor at which AVP is active in the anterior pituitary. Chronic stress paradigms, associated with HPA hyperresponsiveness, and ACTH release following a novel superimposed stress, have been found with relative consistency to show a shift in the CRH:AVP ratio. This may relate to differing feedback sensitivity of AVP to glucocorticoid feedback restraint and the greater responsivity of AVP over CRH to chronic stimulatory stress input. Evidence for functionally distinct pools of ACTH releasing corticotropes, and the finding that AVP levels more closely correlate with ACTH levels than do CRH levels, suggest a more dynamic role for AVP in activity of the stress axis, and a primarily permissive function for CRH. The renewed interest in the role of VP in HPA axis activity may have important implications for furthering our understanding of psychiatric conditions such as depression, where significant dysregulation of this axis is seen. Elevated baseline cortisol, dexamethasone non-suppression and blunted CRH/ACTH release have been consistently documented. The possible contribution of VP to this hyperactivity, despite its known synergy with CRH, has been largely neglected. In animal models there is clear evidence that chronic psychological stressors increase the ratio of AVP to CRH production. Psychosocial stressors are intrinsically linked with depressive illness. The finding of elevated levels of AVP in postmortem studies of depressives and the lowering of CSF AVP levels by antidepressants, raises the question of the precise role of AVP in the overactivity of the HPA in depression, a finding that is currently attributed to overdrive of its HPA regulatory companion, CRH.
探讨了精氨酸加压素（AVPNP）在促肾上腺皮质激素（ACTH）分泌调控中的作用，特别是其在各种应激反应模式中的参与情况，这可能与我们对抑郁症病理生理学的理解相关。VP从下丘脑的两个部位释放；室旁核（PVN）的小细胞部，促肾上腺皮质激素释放激素（CRH）也在此形成，以及视上核（SON）和PVN的大细胞神经元。概述了其与另一种主要的ACTH促分泌素CRH以及糖皮质激素（下丘脑 - 垂体 - 肾上腺轴（HPA）活动的抑制性反馈成分）的复杂相互作用。VP在应激反应中起重要作用现已毋庸置疑。分子生物学技术的进展促进了对心理应激源对下丘脑和垂体水平VP和CRH差异表达影响的研究。重要的是V1b受体基因的克隆，AVP在前垂体中发挥作用的受体。与HPA高反应性相关的慢性应激模式以及新的叠加应激后ACTH的释放，相对一致地发现CRH:AVP比值发生了变化。这可能与AVP对糖皮质激素反馈抑制的不同反馈敏感性以及AVP比CRH对慢性刺激应激输入的更大反应性有关。促肾上腺皮质激素释放促肾上腺皮质激素存在功能上不同池的证据，以及AVP水平比CRH水平与ACTH水平更密切相关的发现，表明AVP在应激轴活动中发挥更动态的作用，而CRH主要起允许作用。对VP在HPA轴活动中作用的重新关注可能对进一步理解抑郁症等精神疾病具有重要意义，在这些疾病中可见该轴的明显失调。基线皮质醇升高、地塞米松不抑制以及CRH/ACTH释放迟钝已得到一致记录。尽管已知VP与CRH具有协同作用，但VP对这种高活性的可能贡献在很大程度上被忽视了。在动物模型中，有明确证据表明慢性心理应激源会增加AVP与CRH产生的比值。心理社会应激源与抑郁症本质上相关。在抑郁症患者的尸检研究中发现AVP水平升高，以及抗抑郁药可降低脑脊液AVP水平，这就提出了AVP在抑郁症中HPA过度活跃的确切作用问题，目前这一现象归因于其HPA调节伴侣CRH的过度驱动。
