Melatonin Promotes Human Hair Follicle Stem Cell Proliferation by Suppressing 5-AR: Implications for Treating Androgenetic Alopecia

Objective: This study explores the influence of melatonin and SRD5A2 on the proliferation and migration of human hair follicle stem cells (hHFSCs), which are vital in the treatment of Androgenic alopecia (AGA), wound healing, and regenerative medicine. Melatonin interacts with various stem cells, including hHFSCs, in multiple ways. Methods: In this study, SRD5A2-silenced hHFSCs were established using shRNA and subsequently cultured with melatonin. The effects on cell proliferation and migration were assessed using Cell Counting Kit-8, EdU-555, and the Transwell Migration Assay, while stemness was determined by assessing CD34 expression by immunohistochemistry. In addition, melatonin receptor 1 (MT1) and 5-alpha-reductase (5-αR) were analyzed using enzyme-linked immunosorbent assay (ELISA) and immunofluorescence microscopy. Results: The results demonstrated that SRD5A2 silencing and melatonin treatment significantly enhanced the proliferation and migration of hHFSCs without causing cell differentiation. Furthermore, this combination led to increased MT1 expression and decreased 5-αR levels. Conclusion: These findings suggest that both melatonin and 5-αR are critical in regulating hHFSCs’ proliferation and migration, with SRD5A2 potentially playing a role in melatonin metabolism by regulating MT1 expression. However, the precise mechanism by which melatonin downregulates 5-αR remains to be elucidated.