The local hypothalamic\u2013pituitary\u2013adrenal axis in cultured human dermal papilla cells

Ji Hyung Chung,Sunghou Lee,Eun Ju Choi,Jinwan Kim,Eun Young Lee,Min Ho Lee,Ji Hae An,Dong Hyun Kim,You Jin Nam,Sangjin Kang,Inbo Han

doi:10.1186/s12860-020-00287-w

Abstract

BackgroundStress 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.ResultsCRF 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.ConclusionThe 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.

Highlights

Stress is an important cause of skin disease, including hair loss
The aims of this study were to determine the CRFinduced modulations in human dermal papilla cells (DPCs) that have a major role Hair follicles (HFs) and investigate whether the local HPA axis is functional in DPCs
corticotropin releasing factor (CRF), a stress hormone, inhibited hair shaft elongation and induced early catagen transition in human HF organ culture To confirm the deleterious effects of CRF on HFs, we exposed anagen-phase human HFs to CRF, and hair shaft elongation and hair cycle transition were monitored

Summary

Introduction

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. The hypothalamic–pituitary–adrenal axis (HPA axis) is a classical system response that plays a role in maintaining stress-related homeostasis. This essential response is activated by various factors, including physical, emotional, and neurological stresses [5]. Corticotropin releasing factor (CRF), adrenocorticotropic hormone (ACTH), and glucocorticoids are crucial stress-related hormones of the HPA axis [6]. After activation through the CRF receptor (CRFR), the anterior pituitary produces proopiomelanocortin (POMC)-derived ACTH, which produces cortisol (human) or glucocorticoids

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