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

Background Effective, safe and well-tolerated therapeutic and/or preventive regimens for chemotherapy-induced alopecia (CIA) still remain to be developed. Because alpha-melanocyte-stimulating hormone (alpha-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 alpha-MSH protects from 4-HC-induced HF dystrophy. Methods Microdissected human scalp HFs from four individuals were treated with 4-HC, alpha-MSH and 4-HC plus alpha-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 alpha-MSH reduced melanin clumping as an early sign of 4-HC-induced disruption of follicular pigmentation. a-MSH reduced 4- HC-induced apoptosis in the HFs of one female patient. These protective effects of alpha-MSH were not associated with changes in 4-HC-induced catagen induction. alpha-MSH and 4-HC both increased HO-1 mRNA expression, while the combination of both agents had additive effects on HO-1 transcription. Conclusions Exogenous alpha-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 alpha-MSH as a candidate CIA-protective agent.