L1.      Effect of thioredoxin reductase 1 on glucocorticoid receptor activity in human outer root sheath cells.
Chang Deok Kim, Kyung Ho Kim, Sunhyae Jang, Dae-Kyoung Choi, Myung Im, Young-Joon Seo, Jeung-Hoon Lee, Jang-Kyu Park, Department of Dermatology, Chungnam National University, Daejeon, Korea

Alopecia areata (AA) is a common disease of patchy hair loss on the scalp that can progress to cover the entire scalp and eventually the entire body. Intralesional injection of corticosteroids is the first-line therapy for adult patients, and it is believed that the effect of glucocorticoid is mediated through the immunosuppressive mechanism primarily. Although it is very powerful treatment for AA, some patients do not respond to glucocorticoid treatment effectively. To delineate the molecular mechanism underlying glucocorticoid insensitivity, we examined the expression of glucocorticoid receptor (GR) and thioredoxin reductase 1 (TrxR1) in AA patients. In some cases of glucocorticoid resistant AA, the expression of TrxR1 was significantly decreased in outer root sheath (ORS). We then investigated the effect of TrxR1 on GR activity using recombinant adenoviruses. The ORS cells were transduced with TrxR1- and GR-expressing adenoviruses together with reporter virus. The results showed that TrxR1 significantly increased GR activity. Next, we determined the effect of TrxR1 on endogenous GR activity of ORS cells. As anticipated, overexpression of TrxR1 markedly increased endogenous GR activity. These results suggest that decreased TrxR1 may lead to the lower responsibility to glucocorticoid treatment via the decreasing GR activity.