Control of human hair growth by neurotrophins: brain-derived neurotrophic factor inhibits hair shaft elongation, induces catagen, and stimulates follicular transforming growth factor beta2 expression

J Invest Dermatol. 2005 Apr;124(4):675-85. doi: 10.1111/j.0022-202X.2005.23648.x.


Neurotrophins are important modulators of epithelial-mesenchymal interactions. Previously, we had shown that brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tyrosine kinase B (TrkB) are prominently involved in the control of murine hair follicle cycling. We now show that BDNF and TrkB are also expressed in the human hair follicle in a manner that is both hair cycle dependent and suggestive of epithelial-mesenchymal cross-talk between BDNF-secreting dermal papilla fibroblasts of anagen hair follicles and subpopulations of TrkB+ hair follicle keratinocytes. As functional evidence for an involvement of BDNF/TrkB in human hair growth control, we show in organ-cultured human anagen hair follicles that 50 ng per mL BDNF significantly inhibit hair shaft elongation, induce premature catagen development, and inhibit keratinocyte proliferation. Quantitative real-time rtPCR analysis demonstrates upregulation of the potent catagen inducer, transforming growth factor beta2 (TGFbeta2) by BDNF, whereas catagen induction by BDNF was partially reversible through co-administration of TGFbeta-neutralizing antibody. This suggests that TrkB-mediated signaling promotes the switch between anagen and catagen at least in part via upregulation of TGFbeta2. Thus, human scalp hair follicles are both a source and target of bioregulation by BDNF, which invites to target TrkB-mediated signaling for therapeutic hair growth modulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / pharmacology
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / pharmacology*
  • Cell Division / drug effects
  • Cell Division / physiology
  • Epithelium / physiology
  • Gene Expression Regulation, Developmental / drug effects
  • Hair Follicle / cytology
  • Hair Follicle / growth & development*
  • Hair Follicle / physiology*
  • Humans
  • Immunohistochemistry
  • Keratinocytes / cytology
  • Keratinocytes / physiology
  • Mesoderm / physiology
  • Organ Culture Techniques
  • RNA, Messenger / analysis
  • Receptor, trkB / genetics
  • Receptor, trkB / metabolism
  • Recombinant Proteins / pharmacology
  • Transcription, Genetic / drug effects
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta2
  • Up-Regulation / drug effects


  • Antibodies
  • Brain-Derived Neurotrophic Factor
  • RNA, Messenger
  • Recombinant Proteins
  • TGFB2 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta2
  • Receptor, trkB