title: α-Melanocyte-stimulating hormone: a protective peptide against chemotherapy-induced hair follicle damage?
abstract: 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.
  
  
  OBJECTIVE
  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 HFs 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 mRNA 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.
authors.affiliation: Department of Dermatology, University of Münster, Von Esmarch-Street 58, D-48149, Münster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Böhm
authors.forename: E
authors.initials: E
authors.lastname: Bodó
authors.forename: W
authors.initials: W
authors.lastname: Funk
authors.forename: R
authors.initials: R
authors.lastname: Paus
mesh_terms: D000505:Alopecia / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D018859:Hair Follicle / Q000187:drug effects* / Q000201:enzymology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D006728:Hormones; D000521:alpha-MSH; C063555:4-hydroperoxydechlorocyclophosphamide; D003520:Cyclophosphamide; D051547:Heme Oxygenase-1