Thesis (Ph.D.)--Chulalongkorn University, 2012

BACKGROUND: Recent studies established that androgen-driven alteration to signals produced by dermal papilla (DP) cells may play an important role in androgenetic alopecia. Here we screened the difference in the protein expression of growth factors/ cytokines in balding vs nonbalding DP cells from the same individuals affected with AGA and found neurotrophins (NTs), namely brain-derived nerve factor (BDNF), neurotrophin (NT)-3 and beta-nerve growth factor (NGF), were the most upregulated protein. OBJECTIVES: To further investigate the effects of four recombinant human (rh) NTs: BDNF, NGF, NT-3 and NT-4 on the proliferation of cultured balding DP cells and hair follicle (HF) growth in vitro. We also assessed whether the neutralizing NTs antibody can reverse the negative effects of NTs. MATERIALS AND METHODS: We evaluated the effects the effects of various concentrations of rhNTs on the proliferation of cultured balding DP cells by MTT assay at day 2 and 4. We also measured elongation of anagen hair follicles in organ culture. Furthermore, the reversible effects of NTs were investigated when the neutralizing NTs antibody was added. RESULTS: NGF, NT-3 and NT-4 at concentration of 10ng/mL and NT-4 at 0.1ng/ mL significantly inhibited proliferation of DP cells at day 2. The more inhibitory effects were observed on day 4, NGF and NT-4 at concentration of 0.1, 1 and 10 ng/ mL showed significantly inhibit DP cells proliferation in dose dependent manner. Moreover, after 10-day of HF organ culture, 1ng/ mL BDNF and NGF significantly inhibited hair shaft growth by 610.2 µm,-44.3% (P=0.003) and 395.7µm, -28.7% (P=0.05), respectively compared with control. Lastly, all NTs neutralizing antibodies failed to reverse NTs-induced cultured DP cells and hair follicles growth inhibition. However, we could observe reversible trend from our results. CONCLUSIONS: NTs produced by balding DP cells inhibit the proliferation of DP cells and human hair follicle growth in vitro. This data, together with the higher expression of NTs in balding compared with nonbalding DP cells suggests that NTs may be one of the key factors involved in pathogenesis of AGA.