Chronic Stress Suppresses the Expression of Cutaneous Hypothalamic–Pituitary–Adrenocortical Axis Elements and Melanogenesis

This study investigated the impact of chronic stress on skin pigmentation, focusing on the cutaneous hypothalamic-pituitary-adrenocortical (HPA) axis and the role of glucocorticoids. Using C57BL/6 male mice exposed to chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS), researchers found that both stress conditions led to reduced melanogenesis and decreased mRNA expression of HPA axis elements in the skin. Administration of corticosterone also resulted in decreased melanin synthesis and reduced expression of HPA axis elements, effects that were reversed by RU486, a glucocorticoid receptor antagonist. The study suggested that chronic stress-induced high levels of serum corticosterone could reduce the expression of skin HPA axis elements through glucocorticoid-dependent negative feedback, leading to decreased skin pigmentation. These findings indicated that chronic stress might be a risk factor for depigmentation and highlighted the need for caution in using glucocorticoids in dermatological treatments.