Development of alopecia areata is associated with higher central and peripheral hypothalamic-pituitary-adrenal tone in the skin graft induced C3H/HeJ mouse model.
1. J Invest Dermatol. 2009 Jun;129(6):1527-38. doi: 10.1038/jid.2008.371. Epub 2008 Nov 20. Development of alopecia areata is associated with higher central and peripheral hypothalamic-pituitary-adrenal tone in the skin graft induced C3H/HeJ mouse model. Zhang X(1), Yu M, Yu W, Weinberg J, Shapiro J, McElwee KJ. Author information: (1)Department of Dermatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China. Comment in J Invest Dermatol. 2009 Jun;129(6):1324-6. doi: 10.1038/jid.2009.111. 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), mineralocorticoid receptor (Nr3c2), corticotropin-releasing hormone receptor types 1 and 2 (Crhr1, Crhr2), interleukin-12 (Il12), tumor necrosis factor-alpha (Tnf alpha), 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. DOI: 10.1038/jid.2008.371 PMCID: PMC4853312 PMID: 19020552 [Indexed for MEDLINE] Conflict of interest statement: CONFLICT OF INTEREST The authors state no conflict of interest.