Stress as a Neuroendocrine Modulator of the Reproductive Axis: Roles of Glucocorticoids, Kisspeptin and Serotonergic Signalling in Animal Models

This review synthesises animal evidence that stress suppresses reproduction through two interacting routes: glucocorticoid action and reduced serotonergic drive on kisspeptin neurons. It identifies the 5-HT7 receptor in arcuate kisspeptin neurons as a likely excitatory link whose loss contributes to stress-induced reproductive dysfunction.

Narrative review — Review. Population: Animal models (species not specified) of stress-related reproductive dysfunction.

This review reports that glucocorticoids act through combined genomic and non-genomic pathways to suppress kisspeptin, GnRH, gonadotropins and gonadal steroidogenesis. Stress suppresses serotonergic signalling by lowering 5-HT levels and suppressing serotonin receptor expression including 5-HT7 receptor, thereby reducing kisspeptin and GnRH neuronal excitation. Glucocorticoid-mediated suppression of kisspeptin signalling, combined with stress-induced reductions in 5-HT and 5-HT receptor expression, suggests a dual suppressive mechanism. No quantitative results are reported.

Researchers working on Kisspeptin would care because this review frames kisspeptin neurons as central integrators of glucocorticoid and serotonergic inputs, and highlights 5-HT7 receptors in arcuate kisspeptin neurons as excitatory regulators of GnRH/LH pulses. It proposes a dual suppressive mechanism of stress on reproduction, but does not establish causality, human relevance, or any therapeutic target.

Key findings

• Glucocorticoids suppress kisspeptin, GnRH, gonadotropin secretion and gonadal steroidogenesis through combined genomic and non-genomic pathways.
• The 5-HT7 receptor is highly expressed in arcuate nucleus kisspeptin neurons and acts as an excitatory driver of GnRH/LH pulse generation.
• Stress lowers 5-HT levels and suppresses serotonin receptor expression, including 5-HT7 receptor, thereby reducing kisspeptin and GnRH neuronal excitation.
• Kisspeptin neurons are crucial integrators of both glucocorticoid and serotonergic signals.
• Combined glucocorticoid-mediated kisspeptin suppression and stress-induced reductions in 5-HT and 5-HT receptor expression suggest a dual suppressive mechanism.

Limitations

• Review based only on animal-model evidence; direct translation to human reproductive dysfunction is uncertain.
• No quantitative synthesis or effect sizes are reported.
• No primary data are presented; conclusions rely on cited literature.
• Species differences in kisspeptin and serotonergic signalling are not addressed in the abstract.

The record

• Journal: Neuroendocrinology: 1-40
• Published: 2026-06-29
• PMID: 42371829 — DOI: 10.1159/000553326

Peptide profiles: Kisspeptin.

All indexed evidence: Kisspeptin trials & papers.

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