Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Peters, E.M. et al.

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 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.[1]

References

A new strategy for modulating chemotherapy-induced alopecia, using PTH/PTHrP receptor agonist and antagonist. Peters, E.M., Foitzik, K., Paus, R., Ray, S., Holick, M.F. J. Invest. Dermatol. (2001) [Pubmed]

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