CRF Receptor Antagonist astressin-B Reverses and Prevents Alopecia in CRF Over-Expressing Mice

PLoS One. 2011 Feb 16;6(2):e16377. doi: 10.1371/journal.pone.0016377.

Abstract

Corticotropin-releasing factor (CRF) signaling pathways are involved in the stress response, and there is growing evidence supporting hair growth inhibition of murine hair follicle in vivo upon stress exposure. We investigated whether the blockade of CRF receptors influences the development of hair loss in CRF over-expressing (OE)-mice that display phenotypes of Cushing's syndrome and chronic stress, including alopecia. The non-selective CRF receptors antagonist, astressin-B (5 µg/mouse) injected peripherally once a day for 5 days in 4-9 months old CRF-OE alopecic mice induced pigmentation and hair re-growth that was largely retained for over 4 months. In young CRF-OE mice, astressin-B prevented the development of alopecia that occurred in saline-treated mice. Histological examination indicated that alopecic CRF-OE mice had hair follicle atrophy and that astressin-B revived the hair follicle from the telogen to anagen phase. However, astressin-B did not show any effect on the elevated plasma corticosterone levels and the increased weights of adrenal glands and visceral fat in CRF-OE mice. The selective CRF₂ receptor antagonist, astressin₂-B had moderate effect on pigmentation, but not on hair re-growth. The commercial drug for alopecia, minoxidil only showed partial effect on hair re-growth. These data support the existence of a key molecular switching mechanism triggered by blocking peripheral CRF receptors with an antagonist to reset hair growth in a mouse model of alopecia associated with chronic stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alopecia / drug therapy*
  • Alopecia / genetics
  • Alopecia / prevention & control*
  • Animals
  • Corticotropin-Releasing Hormone / administration & dosage
  • Corticotropin-Releasing Hormone / genetics*
  • Corticotropin-Releasing Hormone / pharmacology
  • Corticotropin-Releasing Hormone / therapeutic use
  • Drug Evaluation, Preclinical
  • Female
  • Hair / drug effects
  • Hair / growth & development
  • Hormone Antagonists / administration & dosage
  • Hormone Antagonists / pharmacology
  • Hormone Antagonists / therapeutic use
  • Injections, Intraperitoneal
  • Injections, Subcutaneous
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology*
  • Peptide Fragments / therapeutic use*
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Up-Regulation

Substances

  • Hormone Antagonists
  • Peptide Fragments
  • Receptors, Corticotropin-Releasing Hormone
  • astressin B
  • Corticotropin-Releasing Hormone