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Norepinephrine Induces β2-adrenergic Receptor-associated Oxidative Stress and Melanocyte Damage in Organ-cultured Human Scalp Hair Follicles: Implications for Vitiligo-associated Poliosis

Year: 2026

Type: article

Abstract: Poliosis in vitiligo is closely linked to loss or dysfunction of melanocytes within hair follicles, but the contribution of adrenergic stress signalling remains poorly understood. We first compared β2-adrenergic receptor immunoreactivity in vitiligo-associated poliosis hair follicles and normally pigmented hair follicles. We then used cultured human scalp hair follicles to examine the temporal effects of 5 μmol/L norepinephrine, with or without the selective β2-adrenergic receptor antagonist ICI-118551, over 1-7 days. Acute norepinephrine exposure (1 day) increased malondialdehyde levels, reduced superoxide dismutase activity, depolarized the mitochondrial membrane, increased 8-hydroxy-2'-deoxyguanosine and reduced B-cell lymphoma 2 immunoreactivity. Longer exposure (5-7 days) increased gamma histone 2 AX and terminal deoxy-nucleotidyl transferase dUTP nick end labelling signals and produced progressive melanocyte ultrastructural injury. Norepinephrine also reduced tyrosinase-related protein 2 and glycoprotein 100 (premelanosome protein, gp100) immunoreactivity, shortened gp100-positive melanocyte dendrites and produced a biphasic change in Masson-Fontana-stained melanin, with an early increase followed by a decline. ICI-118551 attenuated these effects. These findings show that sustained norepinephrine exposure damages the pigmentation of healthy human scalp hair follicles through a pathway involving β2-adrenergic receptor, oxidative stress, DNA damage and apoptosis. Because functional experiments were not performed in vitiligo hair follicles, the relevance of this pathway to vitiligo-associated poliosis remains to be further researched.

Source: Acta Dermato Venereologica

DOI: 10.2340/actadv.v106.adv-2025-0122