The local hypothalamic–pituitary–adrenal axis in cultured human dermal papilla cells

Abstract

Background Stress is an important cause of skin disease, including hair loss. The hormonal response to stress is due to the HPA axis, which comprises hormones such as corticotropin releasing factor (CRF), adrenocorticotropic hormone (ACTH), and cortisol. Many reports have shown that CRF, a crucial stress hormone, inhibits hair growth and induces hair loss. However, the underlying mechanisms are still unclear. The aim of this study was to examine the effect of CRF on human dermal papilla cells (DPCs) as well as hair follicles and to investigate whether the HPA axis was established in cultured human DPCs. Results CRF inhibited hair shaft elongation and induced early catagen transition in human hair follicles. Hair follicle cells, both human DPCs and human ORSCs, expressed CRF and its receptors and responded to CRF. CRF inhibited the proliferation of human DPCs through cell cycle arrest at G2/M phase and induced the accumulation of reactive oxygen species (ROS). Anagen-related cytokine levels were downregulated in CRF-treated human DPCs. Interestingly, increases in proopiomelanocortin (POMC), ACTH, and cortisol were induced by CRF in human DPCs, and antagonists for the CRF receptor blocked the effects of this hormone. Conclusion The results of this study showed that stress can cause hair loss by acting through stress hormones. Additionally, these results suggested that a fully functional HPA axis exists in human DPCs and that CRF directly affects human DPCs as well as human hair follicles under stress conditions.

Proopiomelanocortin (POMC) and psychodermatology

“…69 The results may also suggest that a fully functional HPA axis exists in human DPCs and that CRF directly affects human DPCs, as well as human HFs, under conditions of stress. 69 Androgenetic alopecia (AGA) is thought to be aggravated by stress too. 70 CRF was used to induce a stress response in human ex vivo male AGA HFs.…”

“…Several reports have shown that CRF inhibits hair growth and induces hair loss 69 . However, the underlying mechanisms are still ambiguous 69 .…”

Stem cell secretome as a mechanism for restoring hair loss due to stress, particularly alopecia areata: narrative review

“…It was shown that prolonged stress can increase inflammatory cytokines (e.g.INF-ɣ) leading to inflammation and ending up in apoptosis, cell senescence and premature catagen transition. DPCs in hair follicle possess receptors for corticotropin releasing factor (CRF) [ 18 ]. When the individual is under stressful events, production of CRF in hypothalamus increases.…”

“…In addition, it accounts for the accumulation of reactive oxygen species (ROS) which also stop the cell cycle. CRF downregulate the expression levels of anagen-related cytokines such as hepatocyte growth factor (HGF), Wnt5a, TGFβ, Vascular endothelial growth factor (VEGF) and versican [ 18 ]. Stress resulting from hair loss contributes to a negative feedback elevating hair loss incidence [ 19 ].…”

Stress and Nasal Allergy: Corticotropin-Releasing Hormone Stimulates Mast Cell Degranulation and Proliferation in Human Nasal Mucosa

“…CRH also exerts multiple other functions, such as inhibiting proliferation and inducing the differentiation of epidermal keratinocytes [ 14 ] stimulating proliferation of dermal fibroblasts and melanocytes [ 15 ], and production of proinflammatory cytokines [ 16 , 17 ]. Importantly, human peripheral tissues also express functional HPA equivalents, including CRH, adrenocorticotropic hormone, and cortisol, and provide negative feedback regulation [ 18 , 19 , 20 , 21 ]. This has been documented best in human skin, where CRH may exert a dual role: short-term pro-inflammatory actions (e.g., via the induction of mast cell (MC) degranulation) and longer lasting immunoinhibitory functions via the stimulation of local cortisol synthesis by keratinocytes [ 12 , 22 ].…”