| 5alpha-dihydrotestosterone (DHT) retards wound closure by inhibiting re-epithelialization. | |
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MedLine Citation:
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PMID: 18855875 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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S C Gilliver; J P D Ruckshanthi; M J Hardman; L A H Zeef; G S Ashcroft |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of pathology Volume: 217 ISSN: 1096-9896 ISO Abbreviation: J. Pathol. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2008-12-16 Completed Date: 2009-02-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0204634 Medline TA: J Pathol Country: England |
Other Details:
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Languages: eng Pagination: 73-82 Citation Subset: IM |
Affiliation:
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Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Androgens
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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:
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GR064256MA//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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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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