Reproduction under Siege: How Chronic Stress Hijacks the HPG Axis?

IF 2.4 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Neuroendocrinology Pub Date : 2026-07-14 DOI:10.1159/000553429

Duo Xu, Xu Zhao, Wanxin Chen, Yi Liu, Chaohu Wang

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引用次数: 0

Abstract

Background: Chronic stress profoundly disrupts homeostasis, with the hypothalamic-pituitary-gonadal (HPG) axis emerging as an active integrator rather than a passive target in stress pathophysiology.

Summary: This review synthesizes evidence that chronic stress acts on the HPG axis at multiple levels: hypothalamic-pituitary-adrenal (HPA)-derived corticotropin-releasing hormone and glucocorticoids suppress the gonadotropin-releasing hormone (GnRH) pulse generator through kisspeptin/KNDy and gonadotropin-inhibitory hormone pathways; sympathetic overdrive impairs gonadal steroidogenesis while parasympathetic tone declines; and metabolic-inflammatory crosstalk amplifies suppression. The resulting decline in sex steroids - estradiol, progesterone, and testosterone - creates sex-specific vicious cycles that further dysregulate stress and immune circuits, contributing to affective, reproductive, and neurodegenerative disorders.

Key messages: The HPG axis serves as a critical hub integrating stress signals, and its suppression is an active, regulated process with distinct sex differences. Hormone-based interventions, including estrogen, neurosteroid analogs, and testosterone, show therapeutic promise for stress-related conditions, and future research should focus on the neural circuits and molecular switches that govern HPA-HPG crosstalk to enable personalized, neuroendocrine-informed therapies.

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围攻下的生殖：慢性压力如何劫持HPG轴。

慢性应激严重破坏体内平衡，下丘脑-垂体-性腺（HPG）轴在病理生理中起着积极的作用。这篇综述综合了证明HPG轴多层次“劫持”的证据。通过CRH和糖皮质激素激活HPA轴，抑制GnRH脉冲发生器，而交感神经流出直接损害性腺甾体生成。因此，性类固醇的减少造成了一个恶性的、性别特异性的适应负荷循环，进一步失调压力和免疫回路。我们通过HPG轴失调重新定义应激相关病理，总结以激素为中心干预的临床证据，将性激素定位为恢复生理和心理健康的关键治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroendocrinology 医学-内分泌学与代谢

CiteScore

8.30

自引率

2.40%

发文量

审稿时长

6-12 weeks

期刊介绍： ''Neuroendocrinology'' publishes papers reporting original research in basic and clinical neuroendocrinology. The journal explores the complex interactions between neuronal networks and endocrine glands (in some instances also immunecells) in both central and peripheral nervous systems. Original contributions cover all aspects of the field, from molecular and cellular neuroendocrinology, physiology, pharmacology, and the neuroanatomy of neuroendocrine systems to neuroendocrine correlates of behaviour, clinical neuroendocrinology and neuroendocrine cancers. Readers also benefit from reviews by noted experts, which highlight especially active areas of current research, and special focus editions of topical interest.