1. ^*Department of Internal Medicine, Biomedical Research Center, University Medicine Charité, Campus Virchow Hospital, Berlin, Germany
2. ^†Department of Dermatology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
3. ^‡Department of Dermatology, Kyoto University, Kyoto, Japan
4. ^§Cutech Srl, Padova, Italy

Correspondence: Eva M. J. Peters, MD, Skin and Hair Research in Psychoneuroimmunology, Department of Internal Medicine, Biomedical Research Center, Room Nr. 2.0549, University Medicine Charité, Campus Virchow Hospital, Augustenburger Platz 1, D-13353, Berlin, Germany. Email: frl_peters@yahoo.com

Received 26 April 2004; Revised 12 August 2004; Accepted 2 September 2004.

Abstract

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 2 (TGF2) by BDNF, whereas catagen induction by BDNF was partially reversible through co-administration of TGF-neutralizing antibody. This suggests that TrkB-mediated signaling promotes the switch between anagen and catagen at least in part via upregulation of TGF2. 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.