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

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 cyclophosphamide in vivo. PTH(7-34) and PTHrP(7-34) shifted it towards a mild form of "dystrophic anagen", associated with a significant 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.

• Authors: E M Peters, K Foitzik, R Paus, S Ray, M F Holick
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 117 Issue 2 Pg. 173-8 (Aug 2001) ISSN: 0022-202X [Print] United States
• PMID: 11511291 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents, Alkylating
• Hormone Antagonists
• Parathyroid Hormone
• Peptide Fragments
• Proteins
• Teriparatide
• parathyroid hormone-related protein (7-34)amide
• Cyclophosphamide
• parathyroid hormone (1-34)amide

Topics

• Alopecia (chemically induced, drug therapy)
• Animals
• Antineoplastic Agents, Alkylating (pharmacology)
• Apoptosis (drug effects)
• Cell Division (drug effects)
• Cyclophosphamide (pharmacology)
• Female
• Hair Follicle (drug effects, pathology)
• Hormone Antagonists (agonists, pharmacology)
• In Situ Nick-End Labeling
• Keratinocytes (drug effects, pathology)
• Mice
• Mice, Inbred C57BL
• Neoplasms (complications, drug therapy)
• Parathyroid Hormone (agonists, antagonists & inhibitors, pharmacology)
• Peptide Fragments (agonists, antagonists & inhibitors, pharmacology)
• Proteins (agonists, antagonists & inhibitors, pharmacology)
• Teriparatide (agonists, analogs & derivatives, antagonists & inhibitors, pharmacology)