P5.47 Human hair follicles display a functional equivalent of the hypothalamic-pituitary-adrenal axis and synthesize cortisol

Natsuho Ito¹, Taisuke Ito^1,2, Arno Kromminga³, Albrecht Bettermann¹, Masahiro Takigawa², and Ralf Paus¹

¹Department of Dermatology, University Hospital Hamburg-Eppendorf, University of Hamburg, Hamburg,  Germany ²Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan ³Institute for Immunology, Clinical Pathology & Molecular Medicine (IPM), Hamburg, Germany

Objectives:It has been proposed that mammalian skin contains a peripheral equivalent of the hypothalamic-pituitary-adrenal (HPA) axis, which controls adrenal cortisol production and serves as a major stress-response regulator and endocrine integrator system in mammalian organisms. Human skin indeed expresses transcripts and/or immunoreactivity (IR) for most of the key components of the HP axis, including corticotropin releasing hormone (CRH) and CRH-receptor (CRH-R), proopiomelanocortin (POMC), alpha-melanocyte stimulating hormone (MSH), adrenocorticotropic hormone (ACTH) and melanocortin receptors and even expresses key enzymes for cortisol synthesis. However, convincing evidence that a functional equivalent of the HPA axis operates in normal skin in situ and that normal human skin actually synthesizes cortisol, is still missing.

Methods: Microdissected, organ-cultured human scalp anagen VI hair follicles were treated with vehicle or recognized key players along the HPA axis (i.e. CRH, or ACTH, or cortisol as the best-established negative feedback signal for hypothalamic CRH secretion) for 2-8 days. We then investigated CRH effects on hair elongation, cell proliferation by Ki67 staining, and connective tissue sheath mast cells by giemsa staining.  In addition, we examined if and how this treatment regimen altered the expression of key HPA axis parameters with immunohistochemistry, RT-PCR and/or in situ hybridization.

Results and Conclusions: This study shows that CRH treated-human scalp hair follicles demonstrated a significant decline in hair shaft elongation and in hair matrix cell proliferation, that CRH may promote the maturation of the connective tissue sheath mast cells, and that human scalp hair follicles display a fully functional equivalent of the HPA axis, synthesize cortisol, and recruit classical HPA feedback loops.