α‐Melanocyte‐stimulating hormone: a protective peptide against chemotherapy‐induced hair follicle damage?

Summary Background Effective, safe and well‐tolerated therapeutic and/or preventive regimens for chemotherapy‐induced alopecia ( CIA ) still remain to be developed. Because α‐melanocyte‐stimulating hormone (α‐ MSH ) exerts a number of cytoprotective effects and is well tolerated, we hypothesized that it may be a candidate CIA ‐protective agent. Objectives To explore, using a human in vitro model for chemotherapy‐induced hair follicle ( HF ) dystrophy that employs the key cyclophosphamide metabolite (4‐hydroperoxy‐cyclophosphamide, 4‐ HC ), whether α‐ MSH protects from 4‐ HC ‐induced HF dystrophy. Methods Microdissected human scalp HF s from four individuals were treated with 4‐ HC , α‐ MSH and 4‐ HC plus α‐ MSH . Changes in HF cycling, melanin distribution and hair matrix keratinocyte proliferation/apoptosis were examined by quantitative (immune‐) morphometry. Expression of the cytoprotective enzyme haem oxygenase‐1 ( HO ‐1) was determined by real‐time reverse transcriptase–polymerase chain reaction in HF of two individuals. Results In 50% of the individuals α‐MSH reduced melanin clumping as an early sign of 4‐HC‐induced disruption of follicular pigmentation. α‐MSH reduced 4‐HC‐induced apoptosis in the HFs of one female patient. These protective effects of α‐MSH were not associated with changes in 4‐HC‐induced catagen induction. α‐MSH and 4‐HC both increased HO‐1 m RNA expression, while the combination of both agents had additive effects on HO‐1 transcription. Conclusions Exogenous α‐ MSH exerts moderate HF ‐protective effects against 4‐ HC ‐induced human scalp HF damage and upregulates the intrafollicular expression of a key cytoprotective enzyme. However, as substantial interindividual response variations were found, further studies are needed to probe α‐ MSH as a candidate CIA ‐protective agent.