Olfactory receptor OR2AT4 regulates human hair growth

Nat Commun. 2018 Sep 18;9(1):3624. doi: 10.1038/s41467-018-05973-0.


Olfactory receptors are expressed by different cell types throughout the body and regulate physiological cell functions beyond olfaction. In particular, the olfactory receptor OR2AT4 has been shown to stimulate keratinocyte proliferation in the skin. Here, we show that the epithelium of human hair follicles, particularly the outer root sheath, expresses OR2AT4, and that specific stimulation of OR2AT4 by a synthetic sandalwood odorant (Sandalore®) prolongs human hair growth ex vivo by decreasing apoptosis and increasing production of the anagen-prolonging growth factor IGF-1. In contrast, co-administration of the specific OR2AT4 antagonist Phenirat® and silencing of OR2AT4 inhibit hair growth. Together, our study identifies that human hair follicles can engage in olfactory receptor-dependent chemosensation and require OR2AT4-mediated signaling to sustain their growth, suggesting that olfactory receptors may serve as a target in hair loss therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis / drug effects
  • Butanols / pharmacology
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Cyclopentanes / pharmacology
  • Epithelium / metabolism
  • Gene Knockdown Techniques
  • Hair Follicle / drug effects
  • Hair Follicle / growth & development*
  • Healthy Volunteers
  • Humans
  • Insulin-Like Growth Factor I / metabolism*
  • Keratinocytes / metabolism
  • Middle Aged
  • Organ Culture Techniques
  • RNA, Small Interfering / metabolism
  • Receptors, Odorant / antagonists & inhibitors
  • Receptors, Odorant / genetics
  • Receptors, Odorant / metabolism*
  • Scalp
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Butanols
  • Cyclopentanes
  • IGF1 protein, human
  • OR2AT4 protein, human
  • RNA, Small Interfering
  • Receptors, Odorant
  • pentamethylcyclopent-3-ene-butanol
  • Insulin-Like Growth Factor I