Alopecia areata and Affected Skin CRH Receptor Upregulation Induced by Acute Emotional Stress

Abstract

Background: Recent evidence indicates that acute stress can precipitate a number of dermatological conditions, including alopecia areata. This effect may be mediated by corticotropin-releasing hormone (CRH) released locally in the skin from dorsal root ganglia or immune cells. CRH typically acts through activation of specific receptors that are either type 1 or types 2α and 2β. CRH, or related peptides such as urocortin, could have proinflammatory effects directly or through activation of mast cells leading to destruction of the hair root. Objectives: To investigate the expression of CRH receptors on the affected skin of patients who developed alopecia areata following acute emotional stress. Methods: Scalp skin biopsies were obtained from 1 normal volunteer and 3 patients after ring infiltration of the relevant site with lidocaine. The biopsies were frozen and were later processed for in situ hybridization for CRH receptors type 1 or types 2α and 2β. Sections showing positive results were photographed. Results: The skin from the normal volunteer showed weak background expression of all three receptor types. However, skin from the affected sites of all 3 patients studied showed intense expression only on the type 2β receptor around the hair follicles. Conclusion: Acute emotional stress may precipitate alopecia areata by activation of overexpressed type 2β CRH receptors around the hair follicles leading to intense local inflammation.

Regulation of corticotropin-releasing hormone receptor-2 expression in human cord blood-derived cultured mast cells

“…These findings indicate that there may be innate ways of regulating CRH-R activation. So far, skin CRH-R2 was shown to be overexpressed at affected areas of alopecia areata (Katsarou-Katsari et al 2001), while skin CRH-R1 was overexpressed in chronic urticaria . Intradermal injection of CRH had been previously reported to induce skin mast cell degranulation and increase vascular permeability, effects absent in W/W v mast cell deficient mice (Theoharides et al 1998).…”

“…Overexpression of CRH-R2 was reported in inflamed subcutaneous tissue (Mousa et al 2003) and in stress-induced alopecia (Katsarou-Katsari et al 2001). Mast cells in the joints of rheumatoid arthritis (RA) patients were shown to express CRH-R (McEvoy et al 2001).…”

Corticotropin releasing hormone and the skin

“…(6,7,20,24,51,70,(72)(73)(74)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95). These studies indicate that human hair follicles are also peripheral endocrine mini-organs that are both a source (including a metabolizing source) and a target of multiple neuro-steroido-hormones (4,74,91,(95)(96)(97)(98).…”

Neuronal plasticity of the “brain–skin connection”: stress-triggered up-regulation of neuropeptides in dorsal root ganglia and skin via nerve growth factor-dependent pathways

“…In general, such stress-response pathways may be considered as a physiological process of adaptation to the demands of the environment; however, an exceeding stress response has been shown to aggravate or trigger chronic diseases in selected individuals, such as exacerbations of inflammatory bowel disease, atopic diseases, or pregnancy complications [1][2][3][4][5]. High perception of stress influences skin immune homeostasis and may contribute to trigger and/or aggravate immune dermatoses such as atopic dermatitis, psoriasis, alopecia areata (AA), or chronic urticaria [6][7][8]. Further, stress perception has been suggested as a cause or aggravating factor of telogen effluvium [9,10].…”