Neuroendocrine mechanisms of stress-induced KNDy-GnRH pulse generator suppression: Linking HPA-axis activation to female reproductive dysfunction.

Authors

Wenjie Bo, Yujing Li, Ruiying Wang, Xinyu Qiao, Yuchan Zhong, Tingting Liu, Jiagui Liang, Huiqiao Lai, Wei Huang

Published in

Frontiers in neuroendocrinology. Pages 101270. Jul 04, 2026. Epub Jul 04, 2026.

Abstract

Chronic stress disrupts female reproductive function, but the central mechanisms linking stress exposure to altered gonadotropin-releasing hormone (GnRH) pulsatility remain incompletely defined. The arcuate kisspeptin/neurokinin B/dynorphin (KNDy) network is a core component of the GnRH pulse generator, yet it functions within an expanded regulatory system involving fast amino-acid neurotransmission, steroid feedback, nitric oxide signaling, glial communication, metabolic cues, and stress-responsive neuropeptides. This review synthesizes evidence showing how hypothalamic-pituitary-adrenal (HPA)-axis activation may suppress KNDy-GnRH output. Corticotropin-releasing hormone, glucocorticoids, gonadotropin-inhibitory hormone/RFamide-related peptide-3, glial inflammatory mediators, serotonergic input, and energy-sensitive neuropeptides may converge to impair GnRH pulse-generator function. We further discuss the relevance of these mechanisms to functional hypothalamic amenorrhea, stress-sensitive polycystic ovary syndrome (PCOS) phenotypes, and developmental versus adult stress exposure. Overall, stress-induced reproductive dysfunction is best understood as disrupted network-level neuroendocrine rhythm regulation.

PMID:
42401315
Bibliographic data and abstract were imported from PubMed on 05 Jul 2026.

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