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

Abstract

Chronic stress can affect skin function, and some skin diseases might be triggered or aggravated by stress. Stress can activate the central hypothalamic–pituitary–adrenocortical (HPA) axis, which causes glucocorticoid levels to increase. The skin has HPA axis elements that react to environmental stressors to regulate skin functions, such as melanogenesis. This study explores the mechanism whereby chronic stress affects skin pigmentation, focusing on the HPA axis, and investigates the role of glucocorticoids in this pathway. We exposed C57BL/6 male mice to two types of chronic stress, chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS). Mice subjected to either stress condition showed reduced melanogenesis. Interestingly, CRS and CUMS triggered reductions in the mRNA expression levels of key factors involved in the HPA axis in the skin. In mice administered corticosterone, decreased melanin synthesis and reduced expression of HPA axis elements were observed. The reduced expression of HPA axis elements and melanogenesis in the skin of stressed mice were reversed by RU486 (a glucocorticoid receptor antagonist) treatment. Glucocorticoids had no significant inhibitory effect on melanogenesis in vitro. These results suggest that, high levels of serum corticosterone induced by chronic stress can reduce the expression of elements of the skin HPA axis by glucocorticoid-dependent negative feedback. These activities can eventually result in decreased skin pigmentation. Our findings raise the possibility that chronic stress could be a risk factor for depigmentation by disrupting the cutaneous HPA axis and should prompt dermatologists to exercise more caution when using glucocorticoids for treatment.

IFNα, a potential biomarker for stress vitiligo risk

“…We as well as other researchers presented evidence that psychiatric stress is an important factor responsible for vitiligo in mice and in human (5, 21, 23, 27). Therefore, we established two types of chronic stress (CRS, CUMS)-induced depressant phenotype and then examined whether chronic stress in animal could affect melanogenic function.…”

“…Previously, we have also found that cutaneous local 5-HT-5-HT1A/1B system, SP/NK1R system and HPA axis were involved in stress-induced depigmentary response (5, 21, 29). We further detected 5-HTR1A/1B, SP and HPA axis expression in skin.…”

“…Neural theory has a wide range of supportive evidence. Abnormalities in both humoral and neurotransmitter (5-HT, SP, CGRP) have been documented (5, 21, 22). In our study, all vitiligo patients were evaluated with Hamiton Depression Scale (HAMD, 24 items) and Hamiton Anxiety Scale (HAMA) by psychiatrists.…”

“…At present, due to the lack of rapid and effective diagnostic indicators used to accurately classify vitiligo patients, clinical treatments often blindly choose surgery or immunosuppression by combination of light therapy. China Vitiligo Treatment Consensus (2014 Edition) categories include: (1) VIDA score, (2) vitiligo Kobner test (KP), (3) clinical characteristics, (4) Woods lamp observation, (5) Skin CT supplementary diagnosis, and (6) skin pathology. The above four points can comprehensively assess the progression of the disease.…”

Hair cortisol in the evaluation of Cushing syndrome

“…(A) Excessive shampoo washings and hair dyeing [28,29] can leach cortisol from hair, and prolonged exposure to UV light causes photo-degradation or cross-linking of glucocorticoid molecules [30], decreasing the quantification of cortisol measured in hair. (B) Assuming that skin has local HPA-like activity and appropriate negative feedback loops [33,36], the production and dynamics of locally-synthesized CRH and ACTH should be negligible under systemic suppression in chronic hypercortisolism as in murine models [47]. As may be seen in adrenal tissue in ACTH-dependent CS, in vitro studies of cultured skin sections have shown doubling to tripling of cortisol production after exposure to ACTH [48].…”