Melanocortin 1 receptor is dispensable for acute stress induced hair graying in mice.

Stress is a risk factor for many skin conditions, but the cellular and molecular mechanisms of its impacts have only begun to be revealed. In mice, acute stress induces loss of melanocyte stem cells (MeSCs) and premature hair greying. Our previous work demonstrated that the loss of MeSCs upon acute stress is caused by the hyperactivation of the sympathetic nervous system. Stress also induces the secretion of stress hormones from the hypothalamic-pituitary-adrenal (HPA) axis; however, whether stress hormones are involved in the hair greying process has not been fully examined. In particular, the adrenocorticotropic hormone (ACTH) is released from the pituitary glands upon stress. ACTH is a ligand for the melanocortin 1 receptor (MC1R), which plays critical roles in regulating MeSC migration and skin pigmentation. We investigated whether the MC1R pathway is required for the stress-induced hair greying. We confirmed that MC1R is the major melanocortin receptor expressed in MeSCs. However, induction of acute stress via resiniferatoxin (RTX) injection still leads to hair greying in Mc1r mutant mice, suggesting that the ACTH-MC1R pathway is not a major contributor in acute stress-induced premature hair greying.