New effects of caffeine on corticotropin-releasing hormone (CRH)-induced stress along the intrafollicular classical hypothalamic-pituitary-adrenal (HPA) axis (CRH-R1/2, IP3-R, ACTH, MC-R2) and the neurogenic non-HPA axis (substance P, p75NTRand TrkA) inex vivohuman male androgenetic scalp hair follicles

Background Human hair is highly responsive to stress, and human scalp hair follicles (HFs) contain a peripheral neuroendocrine equivalent of the systemic hypothalamic-pituitary-adrenal (HPA) stress axis. Androgenetic alopecia (AGA) is supposed to be aggravated by stress. We used corticotropin-releasing hormone (CRH), which triggers theHPAaxis, to induce a stress response in humanex vivomaleAGA HFs. Caffeine is known to reverse testosterone-mediated hair growth inhibition in the same hair organ culture model. Objectives To investigate whether caffeine would antagonizeCRH-mediated stress in theseHFs. Methods HFs from balding vertex area scalp biopsies of men affected byAGAwere incubated withCRH(10(-7)mol L-1) with or without caffeine (0 center dot 001% or 0 center dot 005%). Results Compared to controls,CRHsignificantly enhanced the expression of catagen-inducing transforming growth factor-beta 2 (TGF-beta 2) (P< 0 center dot 001),CRHreceptors 1 and 2 (CRH-R1/2) (P< 0 center dot 01), adrenocorticotropic hormone (ACTH) (P< 0 center dot 001) and melanocortin receptor 2 (MC-R2) (P< 0 center dot 001), and additional stress-associated parameters, substance P and p75 neurotrophin receptor (p75(NTR)).CRHinhibited matrix keratinocyte proliferation and expression of anagen-promoting insulin-like growth factor-1 (IGF-1) and the pro-proliferative nerve growth factor receptor NGF-tyrosine kinase receptor A (TrkA). Caffeine significantly counteracted all described stress effects and additionally enhanced inositol trisphosphate receptor (IP3-R), for the first time detected in humanHFs. Conclusions These findings provide the first evidence inex vivohumanAGA HFs that the stress mediatorCRHinduces not only a complex intrafollicularHPAresponse, but also a non-HPA-related stress response. Moreover, we show that these effects can be effectively antagonized by caffeine. Thus, these data strongly support the hypothesis that stress can impair human hair physiology and induce hair loss, and that caffeine may effectively counteract stress-induced hair damage and possibly prevent stress-induced hair loss. What is already known about this topic? Caffeine stimulates hair growth in male and female human hair follicles (HFs)in vitro. What does this study add? For the first time, corticotropin-releasing hormone induction of the hypothalamic-pituitary-adrenal (HPA) stress axis is documented in male human HFs from biopsies (balding vertex area) of men with androgenetic alopecia. First time, the non-HPA neurogenic stress axis is shown in the same male human HFs. Caffeine counteracts both stress axes. Inositol trisphosphate receptor was newly identified in human HFs. What is the translational message? Stress can impair human hair physiology and induce hair loss. Caffeine may effectively counteract stress-induced hair damage and possibly prevent stress-induced hair loss.

Automated summary

This study demonstrates that CRH induces complex intrafollicular HPA response and non-HPA-related stress response in human AGA HFs, which can be effectively antagonized by caffeine. Additionally, caffeine enhances the expression of inositol trisphosphate receptor, newly detected in human HFs, supporting the hypothesis that stress can impair human hair physiology and induce hair loss, and caffeine may prevent stress-induced hair damage and loss.