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The sex steroid precursor DHEA accelerates cutaneous wound healing via the estrogen receptors

Mills, Stuart J. and Ashworth, Jason J. and Gilliver, Stephen C. and Hardman, Matthew J. and Ashcroft, Gillian S. (2005) The sex steroid precursor DHEA accelerates cutaneous wound healing via the estrogen receptors. ISSN 1523-1747

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Abstract

Age-related impaired wound healing states lead to substantial morbidity and cost, with treatment in the USA resulting in an expenditure of over $9 billion per annum. Dehydroepiandrosterone (DHEA) is a ubiquitous adrenal hormone with immunomodulatory properties whose levels decline significantly with advanced age in humans. Conversion of DHEA locally to downstream steroid hormones leads to estrogenic and/or androgenic effects which may be important in age-related skin homeostasis, and which would avoid systemic adverse effects related to estrogen. We report that systemic DHEA levels are strongly associated with protection against chronic venous ulceration in humans. DHEA accelerated impaired healing in an impaired healing model (mice rendered hypogonadal) associated with increased matrix deposition and dampens the exaggerated inflammatory response. Such effects were mediated by local conversion of DHEA to estrogen, acting through the estrogen receptor, and vitro studies suggest a direct effect on specific pro-inflammatory cytokine production by macrophages via mitogen activated kinase (MAP) and phosphatidylinositol 3 (PI3) kinase pathways. In addition, we show that local injection of DHEA accelerates impaired healing in an ageing mouse colony. We suggest that exogenous application of DHEA accelerates impaired wound repair, results which may be applicable to the prophylaxis and treatment of human impaired wound healing states.

Item Type: Article
Additional Information: Full-text of this article is not available in this e-prints service. This article was originally published [following peer-review] in The Journal of Investigative Dermatology, published by and copyright Nature Publishing Group.
Divisions: Legacy Research Institutes > Research Institute for Health and Social Change > Social Change and Well Being
Date Deposited: 11 Jan 2010 13:57
Last Modified: 01 Sep 2016 13:57
URI: http://e-space.mmu.ac.uk/id/eprint/89142

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