Mechanism of Action of Minoxidil in the Treatment of Androgenetic Alopecia Is Likely Mediated by Mitochondrial Adenosine Triphosphate Synthase-Induced Stem Cell Differentiation

J Biol Regul Homeost Agents. Oct-Dec 2017;31(4):1049-1053.

Abstract

Topical minoxidil is the only topical drug approved by the US Food and Drug Administration (FDA) for the treatment of androgenetic alopecia. However, the exact mechanism by which minoxidil stimulates anagen phase and promotes hair growth is not fully understood. In the late telegen phase of the hair follicle growth cycle, stem cells located in the bulge region differentiate and re-enter anagen phase, a period of growth lasting 2-6 years. In androgenetic alopecia, the anagen phase is shortened and a progressive miniaturization of hair follicles occurs, eventually leading to hair loss. Several studies have demonstrated that minoxidil increases the amount of intracellular Ca2+, which has been shown to up-regulate the enzyme adenosine triphosphate (ATP) synthase. A recent study demonstrated that ATP synthase, independent of its role in ATP synthesis, promotes stem cell differentiation. As such, we propose that minoxidil induced Ca2+ influx can increase stem cell differentiation and may be a key factor in the mechanism by which minoxidil facilitates hair growth. Based on our theory, we provide a roadmap for the development of a new class of drugs for the treatment of androgenetic alopecia.

MeSH terms

  • Adult
  • Alopecia / drug therapy*
  • Alopecia / enzymology
  • Alopecia / genetics
  • Alopecia / pathology
  • Calcium / metabolism
  • Cell Differentiation / drug effects
  • Gene Expression
  • Hair Follicle / drug effects*
  • Hair Follicle / enzymology
  • Hair Follicle / pathology
  • Humans
  • Ion Transport / drug effects
  • Male
  • Middle Aged
  • Minoxidil / therapeutic use*
  • Mitochondria / drug effects*
  • Mitochondria / enzymology
  • Mitochondrial Proton-Translocating ATPases / genetics*
  • Mitochondrial Proton-Translocating ATPases / metabolism
  • Stem Cells / drug effects*
  • Stem Cells / enzymology
  • Stem Cells / pathology
  • Up-Regulation
  • Vasodilator Agents / therapeutic use*

Substances

  • Vasodilator Agents
  • Minoxidil
  • Mitochondrial Proton-Translocating ATPases
  • Calcium