Luteinizing Hormone Induces Murine Hair Loss through Transient Receptor Potential Canonical Channel-Mediated Cell Aging Responses: Implications for Female Pattern Hair Loss Pathogenesis

Menopause-related hormonal imbalances, particularly the decline in estrogen and the rise in luteinizing hormone (LH), are implicated in female-pattern hair loss (FPHL). This study investigated the role of LH in FPHL, because its precise function has remained unclear. Our results found a significant association between elevated LH levels and FPHL. The binding of LH to LH receptor activates downstream transient receptor potential canonical channels (TRPCs), which potentially mediate excess calcium ion signals to initiate cell-aging responses. We revealed that LH causes ROS accumulation, calcium ion elevation and senescence in vibrissa follicles, and cell damage through DNA damage response, senescence, and senescence-associated secretory phenotype activation in dermal papilla cells. Hair loss in mice was due to LH-induced hair follicle damage and aging. The involvement of TRPCs in LH-induced pathogenesis was examined by treatment with TRPC inhibitors. Similarly, the balding area of FPHL showed higher levels of LH receptor than the nonbalding area, whereas expressions of DNA damage response-related genes, senescence-associated secretory phenotype-related genes, and TRPCs were upregulated in scalp biopsies. Overall, we identified the impacts of LH/LH receptor signaling on the pathogenesis of FPHL, including TRPC-mediated cell-aging responses in hair follicles.