Document Detail


5alpha-dihydrotestosterone (DHT) retards wound closure by inhibiting re-epithelialization.
MedLine Citation:
PMID:  18855875     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 5alpha-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 beta-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.
Authors:
S C Gilliver; J P D Ruckshanthi; M J Hardman; L A H Zeef; G S Ashcroft
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pathology     Volume:  217     ISSN:  1096-9896     ISO Abbreviation:  J. Pathol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-16     Completed Date:  2009-02-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  73-82     Citation Subset:  IM    
Affiliation:
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
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MeSH Terms
Descriptor/Qualifier:
Androgens / pharmacology*
Animals
Cell Movement / drug effects
Cells, Cultured
Dihydrotestosterone / metabolism,  pharmacology*
Enzyme Inhibitors / pharmacology
Epidermis / drug effects
Epithelium / drug effects,  metabolism
Finasteride / analogs & derivatives,  pharmacology
Keratinocytes / drug effects,  physiology
Male
Rats
Rats, Sprague-Dawley
Skin / drug effects,  injuries,  metabolism
Testosterone 5-alpha-Reductase / antagonists & inhibitors
Wound Healing / drug effects*,  physiology
beta Catenin / metabolism
Grant Support
ID/Acronym/Agency:
GR064256MA//Wellcome Trust
Chemical
Reg. No./Substance:
0/Androgens; 0/Catnb protein, rat; 0/Enzyme Inhibitors; 0/beta Catenin; 134067-56-4/MK 0434; 521-18-6/Dihydrotestosterone; 98319-26-7/Finasteride; EC 1.3.99.5/Testosterone 5-alpha-Reductase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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