1. ¹Department of Dermatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
2. ²Department of Cellular and Physiological Sciences, The University of British Columbia, Vancouver, BC, Canada
3. ³Department of Dermatology and Skin Science, The University of British Columbia, Vancouver, BC, Canada
4. ⁴Vancouver Coastal Health Research Institute, Vancouver, BC, Canada

Correspondence: Dr Kevin J. McElwee, Department of Dermatology and Skin Science, The University of British Columbia, 835 West Tenth Avenue, Vancouver, BC V5Z 4E8, Canada. E-mail: kevin@keratin.com

Received 13 March 2008; Revised 23 September 2008; Accepted 5 October 2008; Published online 20 November 2008.

Abstract

The relationship of the stress response to the pathogenesis of alopecia areata (AA) was investigated by subjecting normal and skin graft-induced, AA-affected C3H/HeJ mice to light ether anesthesia or restraint stress. Plasma corticosterone (CORT), adrenocorticotropic hormone (ACTH), and estradiol (E2) levels were determined by RIA, whereas gene expression in brains, lymphoid organs, and skin was measured by quantitative RT-PCR for corticotropin-releasing hormone (Crh), arginine vasopressin (Avp), proopiomelanocortin (Pomc), glucocorticoid receptor (Nr3c1), mineralo corticoid receptor (Nr3c2), corticotropin-releasing hormone receptor types 1 and 2 (Crhr1, Crhr2), interleukin-12 (Il12), tumor necrosis factor- (Tnf), and estrogen receptors type-1 (Esr1) and type-2 (Esr2). AA mice had a marked increase in hypothalamic–pituitary–adrenal (HPA) tone and activity centrally, and peripherally in the skin and lymph nodes. There was also altered interaction between the adrenal and gonadal axes compared with that in normal mice. Stress further exacerbated changes in AA mouse HPA activity both centrally and peripherally. AA mice had significantly blunted CORT and ACTH responses to acute ether stress (physiological stressor) and a deficit in habituation to repeated restraint stress (psychological stressor). The positive correlation of HPA hormone levels with skin Th1 cytokines suggests that altered HPA activity may occur as a consequence of the immune response associated with AA.