DHEA and wound repair

James Michael Howard · medicine forum addict Joined: 30 Apr 2005 Posts: 78

J Invest Dermatol. 2005 Nov;125(5):1053-62.

The Sex Steroid Precursor DHEA Accelerates Cutaneous Wound Healing Via the
Estrogen Receptors.

Mills SJ, Ashworth JJ, Gilliver SC, Hardman MJ, Ashcroft GS.

Faculty of Life Sciences, Michael Smith Building, Manchester, UK.

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.

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