[HTML][HTML] Androgen receptor–mediated inhibition of cutaneous wound healing

GS Ashcroft, SJ Mills - The Journal of clinical investigation, 2002 - Am Soc Clin Investig
GS Ashcroft, SJ Mills
The Journal of clinical investigation, 2002Am Soc Clin Investig
Impaired wound healing states in the elderly lead to substantial morbidity, mortality, and a
cost to the USHealth Services of over $9 billion per annum. In addition to intrinsic aging per
se causing delayed healing, studies have suggested marked sex-differences in wound
repair. We report that castration of male mice results in a striking acceleration of local
cutaneous wound healing, and is associated with a reduced inflammatory response and
increased hair growth. Using a hairless mouse model, we have demonstrated that …
Impaired wound healing states in the elderly lead to substantial morbidity, mortality, and a cost to the USHealth Services of over $9 billion per annum. In addition to intrinsic aging per se causing delayed healing, studies have suggested marked sex-differences in wound repair. We report that castration of male mice results in a striking acceleration of local cutaneous wound healing, and is associated with a reduced inflammatory response and increased hair growth. Using a hairless mouse model, we have demonstrated that testosterone reduction stimulates the healing response not through hair follicle epithelial/mesenchymal cell proliferation, but directly via effects on wound cell populations. We suggest that endogenous testosterone inhibits the cutaneous wound healing response in males and is associated with an enhanced inflammatory response. The mechanisms underlying the observed effects involve a direct upregulation of proinflammatory cytokine expression by macrophages in response to testosterone. Blockade of androgen action systemically, via receptor antagonism, accelerates healing significantly, suggesting a specific target for future therapeutic intervention in impaired wound healing states in elderly males.
The Journal of Clinical Investigation