Preventable effect of L-threonate, an ascorbate metabolite, on androgen-driven balding via repression of dihydrotestosterone-induced dickkopf-1 expression in human hair dermal papilla cells

BMB Rep. 2010 Oct;43(10):688-92. doi: 10.5483/BMBRep.2010.43.10.688.

Abstract

In a previous study, we recently claimed that dihydrotestosterone (DHT)-inducible dickkopf-1 (DKK-1) expression is one of the key factors involved in androgen-potentiated balding. We also demonstrated that L-ascorbic acid 2-phosphate (Asc 2-P) represses DHT-induced DKK-1 expression in cultured dermal papilla cells (DPCs). Here, we investigated whether or not L-threonate could attenuate DHT-induced DKK-1 expression. We observed via RT-PCR analysis and enzyme-linked immunosorbent assay that DHT-induced DKK-1 expression was attenuated in the presence of L-threonate. We also found that DHT-induced activation of DKK-1 promoter activity was significantly repressed by L-threonate. Moreover, a co-culture system featuring outer root sheath (ORS) keratinocytes and DPCs showed that DHT inhibited the growth of ORS cells, which was then significantly reversed by L-threonate. Collectively, these results indicate that L-threonate inhibited DKK-1 expression in DPCs and therefore is a good treatment for the prevention of androgen-driven balding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alopecia / chemically induced
  • Alopecia / genetics
  • Alopecia / pathology
  • Alopecia / prevention & control*
  • Androgens / adverse effects
  • Ascorbic Acid / metabolism
  • Butyrates / metabolism
  • Butyrates / pharmacology*
  • Cells, Cultured
  • Chemoprevention / methods
  • Coculture Techniques
  • Dermis / drug effects*
  • Dermis / metabolism
  • Dermis / pathology
  • Dihydrotestosterone / pharmacology*
  • Down-Regulation / drug effects
  • Drug Evaluation, Preclinical
  • Gene Expression Regulation / drug effects
  • Hair Follicle / drug effects*
  • Hair Follicle / metabolism
  • Hair Follicle / pathology
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Male

Substances

  • Androgens
  • Butyrates
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Dihydrotestosterone
  • threonic acid
  • Ascorbic Acid