Hair follicle stem cell differentiation is inhibited through cross-talk between Wnt/β-catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia

Br J Dermatol. 2012 May;166(5):1035-42. doi: 10.1111/j.1365-2133.2012.10856.x.


Background: Hair follicle (HF) regeneration begins when signals from the mesenchyme-derived dermal papilla cells (DPC) reach multipotent epidermal stem cells in the bulge region. Wnt/β-catenin signalling is known to affect mammalian hair growth positively. In androgenetic alopecia (AGA), androgens cause HF miniaturization through a mechanism that remains unclear. Circulating androgens act on DPC and alter paracrine factors that influence hair epithelial cells.

Objectives: To elucidate the role of androgens in dermal papilla-induced differentiation of HF stem cells.

Methods: HF stem cell differentiation was evaluated in a coculture model with DPC or culturing with media conditioned by DPC after activation of androgen and Wnt/β-catenin signalling pathways. To study the molecular cross-talk between the androgen and Wnt signalling pathway in DPC, we analysed the expression and activation of downstream Wnt signalling molecules in the presence of androgens.

Results: In a coculture model with human DPC from patients with AGA and HF stem cells, we observed that androgens abrogate hair differentiation evaluated by hair-specific keratin 6 expression. Wnt signalling activation restored the ability of androgen-treated DPC to induce differentiation. Androgen treatment revealed a significant decrease in the cytoplasmic/total β-catenin protein ratio and upregulation of the activity of glycogen synthase kinase-3β in DPC, indicative of canonical Wnt pathway inhibition.

Conclusions: These results suggest that androgens deregulate DPC-secreted factors involved in normal HF stem cell differentiation via the inhibition of the canonical Wnt signalling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alopecia / pathology*
  • Androgens / pharmacology
  • Androgens / physiology*
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • DNA, Complementary / biosynthesis
  • Dermis / pathology
  • Dihydrotestosterone / pharmacology
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Hair Follicle / pathology
  • Humans
  • Keratins, Hair-Specific / metabolism
  • Keratins, Type II / metabolism
  • Lithium Chloride / pharmacology
  • Male
  • RNA / isolation & purification
  • Real-Time Polymerase Chain Reaction
  • Receptors, Androgen / physiology
  • Scalp / metabolism
  • Stem Cells / pathology*
  • Transfection
  • Wnt Signaling Pathway / physiology*


  • Androgens
  • DNA, Complementary
  • KRT75 protein, human
  • Keratins, Hair-Specific
  • Keratins, Type II
  • Receptors, Androgen
  • Dihydrotestosterone
  • RNA
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • Lithium Chloride