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

Parathyroid hormone (PTH) related peptide (PTHrP) and the PTH/PTHrP recepto r (PTH/PTHrP-R) show prominent cutaneous expression, where this signaling s ystem may exert important paracrine and/or autocrine functions, such as in hair growth control. Chemotherapy-induced alopecia one of the fundamental u nsolved problems of clinical oncology - is driven in part by defined abnorm alities in hair follicle cycling. We have therefore explored the therapeuti c potential of a PTH/PTHrP-R agonist and two PTH/PTHrP-R antagonists in a m ouse model of cyclophosphamide-induced alopecia. Intraperitoneal administra tion 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 ana gen", associated with a significant reduction in apoptotic (TUNEL+) hair bu lb cells, thus mitigating the degree of follicle damage and retarding the o nset of cyclophosphamide-induced alopecia. PTH(1-34), in contrast, forced h air follicles into "dystrophic catagen", associated with enhanced intrafoll icular apoptosis. We had previously shown that an induced shift in the foll icular damage-response towards "dystrophic catagen" mitigates cyclophospham ide-induced alopecia, whereas a shift towards "dystrophic catagen" initiall y enhanced the hair loss, yet subsequently promoted accelerated hair follic le recovery. Therefore, this study in an established animal model of chemot herapy-induced alopecia, which closely mimics human chemotherapy-induced al opecia, strongly encourages the exploration of PTH/PTHrP-R agonists and ant agonists as novel therapeutic agents in chemotherapy-induced alopecia.