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 journalArticle

38 Citations (Scopus)

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 - Jan 1 2001
Externally publishedYes

Fingerprint

Parathyroid Hormone Receptor Type 1
Parathyroid Hormone-Related Protein
Chemotherapy
Alopecia
Parathyroid Hormone
Cyclophosphamide
Drug Therapy
Hair Follicle
Dimethoate
Oncology
Hair
Animals
Apoptosis
Recovery
Medical Oncology
Peptide Hormones
In Situ Nick-End Labeling
Animal Models
Skin
parathyroid hormone (7-34)

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

A new strategy for modulating chemotherapy-induced alopecia, using PTH/PTHrP receptor agonist and antagonist. / Peters, Eva M.J.; Foitzik, Kerstin; Paus, Ralf; Ray, Swapna; Holick, Michael F.

In: Journal of Investigative Dermatology, Vol. 117, No. 2, 01.01.2001, p. 173-178.

Research output: Contribution to journalArticle

Peters, Eva M.J. ; Foitzik, Kerstin ; Paus, Ralf ; Ray, Swapna ; Holick, Michael F. / A new strategy for modulating chemotherapy-induced alopecia, using PTH/PTHrP receptor agonist and antagonist. In: Journal of Investigative Dermatology. 2001 ; Vol. 117, No. 2. pp. 173-178.
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