¹Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Korea

Correspondence: Dr Young Kwan Sung or Dr Jung Chul Kim, Department of Immunology, School of Medicine, Kyungpook National University, 2-101 Dong-In-Dong, Chung-Gu, Daegu 700-422, Korea. E-mail: ysung@knu.ac.kr or jayckim@knu.ac.kr

Received 5 February 2007; Revised 28 May 2007; Accepted 4 June 2007; Published online 26 July 2007.

Abstract

Recent studies suggest that androgen-driven alteration to the autocrine and paracrine factors produced by scalp dermal papilla (DP) cells may be a key to androgen-potentiated balding. Here, we screened dihydrotestosterone (DHT)-regulated genes in balding DP cells and found that dickkopf 1 (DKK-1) is one of the most upregulated genes. DKK-1 messenger RNA is upregulated in 3–6 hours after 50–100 nM DHT treatment and ELISA showed that DKK-1 is secreted from DP cells in response to DHT. A co-culture system using outer root sheath (ORS) keratinocytes and DP cells showed that DHT inhibits the growth of ORS cells, and neutralizing antibody against DKK-1 significantly reversed the growth inhibition of ORS cells. Analysis of co-cultured ORS cells showed a significant increment of sub-G1 apoptotic cells in response to DHT. Also, recombinant human DKK-1 inhibited the growth of ORS cells and triggered apoptotic cell death. In addition, DHT-induced epithelial cell death in cultured hair follicles was reversed by neutralizing DKK-1 antibody. Moreover, immunoblotting showed that the DKK-1 level is up in the bald scalp compared with the haired scalp of patients with androgenetic alopecia. Altogether, our data strongly suggest that DHT-inducible DKK-1 is involved in DHT-driven balding.