Nazarloo Hans P, Kingsbury Marcy A, Lamont Hannah, Dale Caitlin V, Nazarloo Parmida, Davis John M, Porges Eric C, Cuffe Steven P, Carter C Sue
Department of Psychiatry, College of Medicine-Jacksonville, University of Florida, 580 West 8th St., Tower II, 6th Floor, Jacksonville, FL 32209, USA.
Lurie Center for Autism, Mass General Research Institute, Harvard Medical School, Charlestown, MA 02129, USA.
Curr Issues Mol Biol. 2025 Aug 7;47(8):632. doi: 10.3390/cimb47080632.
The purpose of this article is to examine a previously unrecognized role for the vasopressin-oxytocin (VP-OT) system in mammalian "stress-response hormesis." The current review adds hormesis to the long list of beneficial effects of OT. Hormesis, a biphasic adaptive response to low-level stressors, is introduced here to contextualize the dynamic roles of oxytocin and vasopressin. As with hormesis, the properties of the VP-OT system are context-, time-, and dose-sensitive. Here we suggest that one key to understanding hormesis is the fact that VP and OT and their receptors function as an integrated system. The VP-OT system is capable of changing and adapting to challenges over time, including challenges necessary for survival, reproduction and sociality. Prior research suggests that many beneficial effects of OT are most apparent only following stressful experiences, possibly reflecting interactions with VP, its receptors and other components of the hypothalamic-pituitary-adrenal axis. The release of OT is documented following various kinds of hormetic experiences such as birth, vigorous exercise, ischemic events and the ingestion of emetics, including psychedelics. The phasic or cyclic modulation of VP and related "stress" hormones, accompanied or followed by the release of OT, creates conditions that conform to the core principles of hormesis. This concept is reviewed here in the context of other hormones including corticotropin releasing hormone (CRH) and urocortin, as well as cytokines. In general, VP and classic "stress hormones" support an active response, helping to quickly mobilize body systems. OT interacts with all of these, and may subsequently re-establish homeostasis and precondition the organism to deal with future stressors. However, the individual history of an organism, including epigenetic modifications of classical stress hormones such as VP, can moderate the effects of OT. Oxytocin's effects also help to explain the important role of sociality in mammalian resilience and longevity. A hormetic perspective, focusing on a dynamic VP-OT system, offers new insights into emotional and physical disorders, especially those associated with the management of chronic stress, and helps us to understand the healing power of social behavior and perceived safety.
本文旨在探讨血管加压素 - 催产素（VP - OT）系统在哺乳动物“应激反应兴奋效应”中一个此前未被认识到的作用。当前的综述将兴奋效应添加到催产素诸多有益作用的长长的列表中。兴奋效应是对低水平应激源的一种双相适应性反应，在此引入它是为了将催产素和血管加压素的动态作用置于相应背景中。与兴奋效应一样，VP - OT系统的特性具有情境、时间和剂量敏感性。在此我们认为，理解兴奋效应的一个关键事实是VP和OT及其受体作为一个整合系统发挥作用。VP - OT系统能够随着时间变化并适应各种挑战，包括生存、繁殖和社交所必需的挑战。先前的研究表明，催产素的许多有益作用仅在经历应激后才最为明显，这可能反映了它与VP、其受体以及下丘脑 - 垂体 - 肾上腺轴其他成分之间的相互作用。在各种兴奋效应经历之后，如出生、剧烈运动、缺血事件以及摄入催吐剂（包括致幻剂）后，都有催产素释放的记录。VP及相关“应激”激素的阶段性或周期性调节，伴随着或随后引发催产素的释放，创造了符合兴奋效应核心原则的条件。在此将结合包括促肾上腺皮质激素释放激素（CRH）、尿皮质素以及细胞因子在内的其他激素来审视这一概念。一般而言，VP和经典“应激激素”支持积极反应，有助于迅速调动身体系统。催产素与所有这些相互作用，随后可能重新建立体内平衡并使机体做好应对未来应激源的准备。然而，生物体的个体经历，包括诸如VP等经典应激激素的表观遗传修饰，能够调节催产素的作用。催产素的作用也有助于解释社交在哺乳动物恢复力和长寿中的重要作用。从兴奋效应的角度出发，聚焦于动态的VP - OT系统，为情绪和身体紊乱，尤其是那些与慢性应激管理相关的紊乱，提供了新的见解，并有助于我们理解社会行为和感知到的安全感的治愈力量。
