Basic Science Department, School of Medicine, Copperbelt University, P.O Box 71191, Ndola, Zambia.
Division of Medical Physiology, Biomedical Science Research Institute, Stellenbosch University, Private Bag X1, Matieland, 7602, Cape Town, South Africa.
Metab Brain Dis. 2024 Dec;39(8):1613-1636. doi: 10.1007/s11011-024-01393-w. Epub 2024 Jul 31.
This comprehensive review explores the intricate relationship between the hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-gonadal (HPG) axis, and aggression. It provides a detailed overview of the physiology and functioning of these axes, as well as the implications for aggressive behavior. The HPA axis, responsible for the stress response, is activated in response to various stressors and can influence aggressive behavior. Glucocorticoids, such as cortisol, play a crucial role in stress-induced activation of the HPA axis and have been implicated in aggressive tendencies. Chronic stress can dysregulate the HPA axis, leading to alterations in cortisol levels and potentially contributing to aggressive behavior. The HPG axis, particularly the androgen hormone testosterone, is also closely linked to aggression. Animal and human studies have consistently shown a positive association between testosterone levels and aggression. The androgen receptors in the brain's neural circuitry play a critical role in modulating aggressive behavior. Interactions between the HPA and HPG axes further contribute to the regulation of aggression. Feedback mechanisms and crosstalk between these axes provide a complex system for the modulation of both stress and reproductive functions, which can impact aggressive behavior. Additionally,the influence of stress on reproductive functions, particularly the role of androgens in stress-induced aggression, adds further complexity to this relationship. The review also discusses the future directions and implications for clinical interventions. Understanding the neurobiological mechanisms underlying aggression requires integrating molecular, cellular, and circuit-level approaches. Translational perspectives, including animal models and human studies, can bridge the gap between basic research and clinical applications. Finally, therapeutic strategies for aggression-related disorders are explored, highlighting the importance of targeted interventions based on a comprehensive understanding of the interactions between the HPA and HPG axes. In conclusion, this review provides a comprehensive overview of the physiological and neurobiological mechanisms underlying aggression, with a specific focus on the interplay between the HPA and HPG axes. By elucidating the complex interactions between stress, hormones, and aggressive behavior, this research paves the way for future investigations and potential therapeutic interventions for aggression-related disorders.
这篇全面综述探讨了下丘脑-垂体-肾上腺（HPA）轴、下丘脑-垂体-性腺（HPG）轴与攻击性之间的复杂关系。它详细介绍了这些轴的生理学和功能，以及它们对攻击性行为的影响。HPA 轴负责应激反应，它会因各种应激源而被激活，并能影响攻击性行为。糖皮质激素（如皮质醇）在应激诱导的 HPA 轴激活中起着至关重要的作用，并且与攻击倾向有关。慢性应激会使 HPA 轴失调，导致皮质醇水平的改变，并可能导致攻击行为。HPG 轴，特别是雄激素睾酮，也与攻击性密切相关。动物和人类研究一致表明，睾酮水平与攻击性之间存在正相关关系。大脑神经回路中的雄激素受体在调节攻击性行为方面起着关键作用。HPA 和 HPG 轴之间的相互作用进一步促进了攻击性的调节。这些轴之间的反馈机制和相互作用提供了一个复杂的系统，用于调节应激和生殖功能，这可能会影响攻击行为。此外，应激对生殖功能的影响，特别是雄激素在应激诱导的攻击中的作用，使这种关系更加复杂。该综述还讨论了未来的研究方向和临床干预的意义。理解攻击性的神经生物学机制需要整合分子、细胞和回路水平的方法。转化视角，包括动物模型和人类研究，可以在基础研究和临床应用之间架起桥梁。最后，探讨了与攻击性相关障碍的治疗策略，强调了基于对 HPA 和 HPG 轴相互作用的全面理解进行有针对性干预的重要性。总之，该综述全面概述了攻击性的生理和神经生物学机制，特别关注了 HPA 和 HPG 轴之间的相互作用。通过阐明应激、激素和攻击性行为之间的复杂相互作用，这项研究为未来对与攻击性相关障碍的研究和潜在的治疗干预铺平了道路。
