A new strategy for modulating chemotherapy-induced alopecia, using PTH/PTHrP receptor agonist and antagonist

Eva M.J. Peters, Kerstin Foitzik, Ralf Paus, Swapna Ray, Michael F. Holick

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Parathyroid hormone (PTH) related peptide (PTHrP) and the PTH/PTHrP receptor (PTH/PTHrP-R) show prominent cutaneous expression, where this signaling system may exert important paracrine and/or autocrine functions, such as in hair growth control. Chemotherapy-induced alopecia-one of the fundamental unsolved problems of clinical oncology-is driven in part by defined abnormalities in hair follicle cycling. We have therefore explored the therapeutic potential of a PTH/PTHrP-R agonist and two PTH/PTHrP-R antagonists in a mouse model of cyclophosphamide-induced alopecia. Intraperitoneal administration of the agonist PTH(1- 34) or the antagonists PTH(7-34) and PTHrP(7-34) significantly altered the follicular response to cyclo-phosphamide in vivo. PTH(7-34) and PTHrP(7-34) shifted it towards a mild form of "dystrophic anagen", associated with a significantcant reduction in apoptotic (TUNEL+) hair bulb cells, thus mitigating the degree of follicle damage and retarding the onset of cyclophosphamide-induced alopecia. PTH(1-34), in contrast, forced hair follicles into "dystrophic catagen", associated with enhanced intrafollicular apoptosis. We had previously shown that an induced shift in the follicular damage-response towards "dystrophic catagen" mitigates cyclophosphamide-induced alopecia, whereas a shift towards "dystrophic catagen" initially enhanced the hair loss, yet subsequently promoted accelerated hair follicle recovery. Therefore, this study in an established animal model of chemotherapy-induced alopecia, which closely mimics human chemotherapy-induced alopecia, strongly encourages the exploration of PTH/PTHrP-R agonists and antagonists as novel therapeutic agents in chemotherapy-induced alopecia.

Original languageEnglish (US)
Pages (from-to)173-178
Number of pages6
JournalJournal of Investigative Dermatology
Volume117
Issue number2
DOIs
StatePublished - Aug 2001
Externally publishedYes

Keywords

  • Cancer therapy
  • Hair loss
  • Parathyroid hormone
  • Parathyroid hormone related peptide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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