Background: C57BL/6 a/a mice have been widely used to study melanogenesis, including in electron paramagnetic resonance (EPR) studies. Zinc cations modulate melanogenesis, but the net effect of Zn2+ in vivo is unclear, as the reported effects of Zn2+ on melanogenesis are ambiguous: zinc inhibits tyrosinase and glutathione reductase in vitro, but also enhances the activity of dopachrome tautomerase (tyrosinase-related protein-2) and has agonistic effects on melanocortin receptor signalling. Objectives: To determine in a C57BL/6 a/a murine pilot study whether excess zinc ions inhibit, enhance or in any other way alter hair follicle melanogenesis in vivo, and to test the usefulness of EPR for this study. Methods: ZnSO4· 7H2O was continuously administered orally to C57BL/6 a/a mice during spontaneous and depilation-induced hair follicle cycling (20 mg mL-1; in drinking water; mean ± SD daily dose 1.2 ± 0.53 mL), and hair pigmentation was examined macroscopically, by routine histology and by EPR. Results: Oral zinc cations induced a bright brown lightening of new hair shafts produced during anagen, but without inducing an EPR-detectable switch from eumelanogenesis to phaeomelanogenesis. The total content of melanin in the skin and hair shafts during the subsequent telogen phase, i.e. after completion of a full hair cycle, was significantly reduced in Zn-treated mice (P = 0.0005). Compared with controls, melanin granules in precortical hair matrix keratinocytes, hair bulb melanocytes and hair shafts of zinc-treated animals were reduced and poorly pigmented. Over the course of several hair cycles, lasting hair shaft depigmentation was seen during long-term exposure to high-dose oral Zn2+. Conclusions: High-dose oral Zn2+ is a potent downregulator of eumelanin content in murine hair shafts in vivo. The C57BL/6 mouse model offers an excellent tool for further dissecting the as yet unclear underlying molecular basis of this phenomenon, while EPR technology is well suited for the rapid, qualitative and quantitative monitoring of hair pigmentation changes.
- Acrodermatitis enteropathica
- Dopachrome tautomerase
- Electron paramagnetic resonance
ASJC Scopus subject areas