5α-Dihydrotestosterone (DHT) retards wound closure by inhibiting re-epithelialization

• Published in: The Journal of pathology Vol. 217; no. 1; pp. 73 - 82
• Main Authors: Gilliver, SC, Ruckshanthi, JPD, Hardman, MJ, Zeef, LAH, Ashcroft, GS
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-01-2009; Wiley
• Subjects: 5α-dihydrotestosterone (DHT); Biological and medical sciences; healing; healing, mice; Investigative techniques, diagnostic techniques (general aspects); keratinocytes; Medical sciences; mice; migration; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; re-epithelialization; skin; wounds; skin; wounds; healing; Rodentia; Wound; Vertebrata; Anatomic pathology; Dihydrotestosterone; Mammalia; Mouse; Animal; Keratinocyte; Skin; Cicatrization; Cell migration; mice; re-epithelialization; keratinocytes; 5α-dihydrotestosterone (DHT); migration
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.2444

The ongoing search for explanations as to why elderly males heal acute skin wounds more slowly than do their female counterparts (and are more strongly disposed to conditions of chronic ulceration) has identified endogenous oestrogens and androgens as being respectively enhancers and inhibitors of repair. We previously demonstrated that blocking the conversion of testosterone to 5α-dihydrotestosterone (DHT) limits its ability to impair healing, suggesting that DHT is a more potent inhibitor of repair than is testosterone. The present study aimed to delineate the central mechanisms by which androgens delay repair. Whilst the contractile properties of neither rat wounds in vivo nor fibroblast-impregnated collagenous discs in vitro appeared to be influenced by androgen manipulations, the global blockade of DHT biosynthesis markedly accelerated re-epithelialization of incisional and excisional wounds and reduced local expression of β-catenin, a key inhibitor of repair. Moreover, DHT retarded the in vitro migration of epidermal keratinocytes following scratch wounding. By contrast, it failed to influence the migratory and proliferative properties of dermal fibroblasts, suggesting that its primary inhibitory effect is upon re-epithelialization. These novel findings may be of particular significance in the context of chronic ulceration, for which being male is a key risk factor. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.