Neuroendocrine Mechanisms in Multiple Sclerosis

Multiple sclerosis (MS) is increasingly recognised as a disorder in which immune-mediated demyelination and neurodegeneration are profoundly influenced by neuroendocrine circuits. Central to this interplay is the hypothalamic–pituitary–adrenal (HPA) axis, which modulates inflammatory activity via glucocorticoid release and shapes immune cell trafficking in the central nervous system. Aberrant HPA axis function in people with MS has been linked to fatigue, mood disturbances and altered stress responses. Parallel disruptions in the hypothalamic–pituitary–gonadal and growth hormone axes contribute to metabolic dysfunction, reproductive hormone imbalances and skeletal health issues commonly observed in MS cohorts. Circadian dysregulation of cortisol secretion and clock gene expression further intersects with immune rhythms, potentially exacerbating disease activity at specific times of day. Neuropeptides released by hypothalamic nuclei, including corticotropin-releasing hormone and arginine vasopressin, act as local immunomodulators, while peripheral endocrine glands respond to inflammatory signals by adjusting steroidogenic pathways. Together, these bidirectional interactions create a feedback network in which neuroendocrine factors both drive and are shaped by CNS autoimmunity. Understanding these mechanisms has prompted exploration of hormone-based interventions, chronotherapeutic strategies and personalised glucocorticoid regimens to ameliorate relapse severity and improve quality of life.

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Neuroendocrine Mechanisms in Multiple Sclerosis publication trend

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Technical terms

HPA axis: Bidirectional network involving the hypothalamus, pituitary gland and adrenal cortex that regulates stress responses and immune activity via glucocorticoid secretion.

Glucocorticoid: Steroid hormone (e.g., cortisol) produced by the adrenal cortex that modulates inflammation and lymphocyte function.

Experimental Autoimmune Encephalomyelitis (EAE): An animal model of MS induced by immunisation to study mechanisms of demyelination and neuroinflammation.

Insulin-like Growth Factor-1 (IGF-1): A peptide hormone produced mainly in the liver that mediates many of the anabolic effects of growth hormone.

Neuropeptide: Short peptide released by neurons that acts as a signalling molecule within neuroendocrine and immune pathways.

References

1. Autoimmune demyelination alters hypothalamic transcriptome and endocrine function. Journal of Neuroinflammation (2024).
2. Experimental Autoimmune Encephalomyelitis Influences GH-Axis in Female Rats. International Journal of Molecular Sciences (2024).
3. Predicting glucocorticoid resistance in multiple sclerosis relapse via a whole blood transcriptomic analysis. CNS Neuroscience & Therapeutics (2023).