Androgen action inactivates canonical Wnt signalling in scalp dermal papilla cells impairing hair follicle stem cell differentiation in androgenetic alopecia

LEIROS G; DEL PRIORE, SABRINA; BALAÑA, MARIA EUGENIA

Congreso; 40th Annual Meeting of the European-Society-for-Dermatological-Research (ESDR 2010) , Helsinki, FINLAND; 2010

European-Society-for-Dermatological-Research

Hair follicle (HF) formation begins when signals from the mesenchyme-derived dermal papilla cells (DPC) reach multipotent epidermal stem cells in the bulge region. In androgenetic alopecia (AGA) androgens action causes HF miniaturization and baldness through a mechanism which remain unclear. Circulating androgens act on  DPC probably by altering the regulatory  paracrine factors involved in the differentiation and proliferation of the HF multipotent cells. The aim of this work is to determine the role of androgens in the differentiation of HF stem cells and to identify the DPC signaling pathways or effector molecules involved in its action. The profile of DPC secreted proteins in response to androgens is modified as revealed by bidimensional gels and HPLC analysis. In a co-culture model with human DPC from patients suffering AGA and HF stem cells, androgens treatment abrogates hair differentiation. The expression of the keratin K6hf, hair differentiation marker, was significantly downregulated in HF stem cells co-cultured with androgen-treated DPC. Association of â-catenin to androgen receptor was observed, indicating that â-catenin is a cofactor of AR signalling in DPC. Androgens significantly upregulate â-catenin expression, both at mRNA and protein levels. Analysis of the cytoplasmic pool by  Western blot showed that the ratio cytoplasmatic/total â-catenin  is significantly lower in androgen-treated DPC showing  that androgens are able to inhibit canonical Wnt signalling in DPC. These results suggest that androgens may modulate the secretion of paracrine factors involved in normal HF stem cell differentiation inactivating the canonical Wnt signaling pathway.