title: Keratinocyte growth inhibition through the modification of Wnt signaling by androgen in balding dermal papilla cells.
abstract: OBJECTIVE
  Androgen induces androgenetic alopecia (AGA), which has a regressive effect on hair growth from the frontal region of the scalp. Conversely, Wnt proteins are known to positively affect mammalian hair growth. We hypothesized that androgen reduces hair growth via an interaction with the Wnt signaling system. The objective of this study was to investigate the effect of androgen on Wnt signaling in dermal papilla (DP) cells.
  
  
  METHODS
  The effect of androgen and Wnt3a on keratinocyte proliferation was measured by use of a coculture system consisting of DP cells and keratinocytes. The molecular mechanisms of androgen and Wnt pathway interactions in DP cells were examined by analyzing the expression, intracellular localization, and activity of the androgen receptor (AR) and also downstream Wnt signaling molecules.
  
  
  RESULTS
  Wnt3a-dependent keratinocyte growth was suppressed by the addition of dihydrotestosterone in coculture with DP cells that were derived from AGA patients, but growth was not suppressed in coculture with DP cells from non-AGA males. Whereas DP cells from both scalp regions expressed AR protein, the expression levels of AR and cotranslocation with beta-catenin, a downstream Wnt signaling molecule, were higher in DP cells of AGA patients than in DP cells from non-AGA males. In addition, significant suppression of Wnt signal-mediated transcription in response to dihydrotestosterone treatment was observed only in DP cells from AGA patients.
  
  
  CONCLUSIONS
  These results suggest that Wnt signaling in DP cells is regulated by androgen and this regulation plays a pivotal role in androgen's action on hair growth.
authors.affiliation: Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kawaramachi Hirokouji, Kyoto, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kitagawa
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Matsuda
authors.forename: Shigeki
authors.initials: S
authors.lastname: Inui
authors.forename: Hideya
authors.initials: H
authors.lastname: Takenaka
authors.forename: Norito
authors.initials: N
authors.lastname: Katoh
authors.forename: Satoshi
authors.initials: S
authors.lastname: Itami
authors.forename: Saburo
authors.initials: S
authors.lastname: Kishimoto
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kawata
mesh_terms: D000328:Adult; D000368:Aged; D000505:Alopecia / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division; D002460:Cell Line; D013196:Dihydrotestosterone / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D011944:Receptors, Androgen / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D012867:Skin / Q000473:pathology / Q000503:physiopathology; D051153:Wnt Proteins / Q000502:physiology*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
chemical_list: D011944:Receptors, Androgen; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D013196:Dihydrotestosterone