Androgens alter dermal papilla secreted factors involved in hair follicle stem cell differentation

GUSTAVO LEIRÓS, SABRINA DEL PRIORE, MARÍA EUGENIA BALAÑÁ

Buenos Aires- Argentina

Simposio; International Symposium on Stem cell Research; 2009

Ministerio de Ciencia, Tecnología e Innovación Productiva / International Society for Stem cell Research

Hair follicle (HF) formation begins when signals from the mesenchyme-derived dermal papilla (DP) reach multipotent epidermal stem cells in the bulge region . The growth of human HF from beard, axillas and scalp is susceptible to androgen action by modulation of DP activity. In androgenetic alopecia (AGA) androgens action causes HF miniaturization and baldness through a mechanism(s) which remain unclear. Circulating androgens act on  DP cells probably by altering the regulatory  paracrine factors involved in the differentiation and proliferation of the HF multipotent cells. Bidimensional gels performed with proteins from conditioned culture media of DP cells revealed differences in the profile of DP secreted protein in response to androgen action. In order to evaluate the role of epithelial-mesenchymal interactions in HF cell differentiation, we established a co-culture model with DP cells from human biopsies of patients suffering AGA and HF stem cell line (Tel E6/E7). The expression levels of K6hf, keratin used as hair differentiation marker, were lower in Tel E6/E7 co-cultured with androgen-treated DP cells, both by western blot and real time PCR.     We conclude that androgens,  modulating the DP secretory activity,  would alter the expression of specific genes involved in normal HF stem cell differentiation, de-regulating its regeneration and inducing miniaturization.    Bidimensional gels performed with proteins from conditioned culture media of DP cells revealed differences in the profile of DP secreted protein in response to androgen action. In order to evaluate the role of epithelial-mesenchymal interactions in HF cell differentiation, we established a co-culture model with DP cells from human biopsies of patients suffering AGA and HF stem cell line (Tel E6/E7). The expression levels of K6hf, keratin used as hair differentiation marker, were lower in Tel E6/E7 co-cultured with androgen-treated DP cells, both by western blot and real time PCR.     We conclude that androgens,  modulating the DP secretory activity,  would alter the expression of specific genes involved in normal HF stem cell differentiation, de-regulating its regeneration and inducing miniaturization.    dermal papilla (DP) reach multipotent epidermal stem cells in the bulge region . The growth of human HF from beard, axillas and scalp is susceptible to androgen action by modulation of DP activity. In androgenetic alopecia (AGA) androgens action causes HF miniaturization and baldness through a mechanism(s) which remain unclear. Circulating androgens act on  DP cells probably by altering the regulatory  paracrine factors involved in the differentiation and proliferation of the HF multipotent cells. Bidimensional gels performed with proteins from conditioned culture media of DP cells revealed differences in the profile of DP secreted protein in response to androgen action. In order to evaluate the role of epithelial-mesenchymal interactions in HF cell differentiation, we established a co-culture model with DP cells from human biopsies of patients suffering AGA and HF stem cell line (Tel E6/E7). The expression levels of K6hf, keratin used as hair differentiation marker, were lower in Tel E6/E7 co-cultured with androgen-treated DP cells, both by western blot and real time PCR.     We conclude that androgens,  modulating the DP secretory activity,  would alter the expression of specific genes involved in normal HF stem cell differentiation, de-regulating its regeneration and inducing miniaturization.    Bidimensional gels performed with proteins from conditioned culture media of DP cells revealed differences in the profile of DP secreted protein in response to androgen action. In order to evaluate the role of epithelial-mesenchymal interactions in HF cell differentiation, we established a co-culture model with DP cells from human biopsies of patients suffering AGA and HF stem cell line (Tel E6/E7). The expression levels of K6hf, keratin used as hair differentiation marker, were lower in Tel E6/E7 co-cultured with androgen-treated DP cells, both by western blot and real time PCR.     We conclude that androgens,  modulating the DP secretory activity,  would alter the expression of specific genes involved in normal HF stem cell differentiation, de-regulating its regeneration and inducing miniaturization.