17beta-estradiol inhibits wound healing in male mice via estrogen receptor-alpha.
Although estrogens have long been known to accelerate healing in females, their roles in males remain to be established. To address this, we have investigated the influence of 17beta-estradiol on acute wound repair in castrated male mice. We report that sustained exposure to estrogen markedly delays wound re-epithelialization. Our use of hairless mice revealed this response to be largely independent of hair follicle cycling, whereas other studies demonstrated that estrogen minimally influences wound inflammation in males. Additionally, we report reduced collagen accumulation and increased gelatinase activities in the wounds of estrogen-treated mice. Increased wound matrix metalloproteinase (MMP)-2 activity in these animals may i) contribute to their inability to heal skin wounds optimally and ii) stem, at least in part, from effects on the overall levels and spatial distribution of membrane-type 1-MMP and tissue inhibitor of MMP (TIMP)-3, which respectively facilitate and prevent MMP-2 activation. Using mice rendered null for either the alpha or beta isoform of the estrogen receptor, we identified estrogen receptor-alpha as the likely effector of estrogen's inhibitory effects on healing.
Gilliver
Stephen C
SC
Faculty of Life Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester M13 9PT, UK.
Emmerson
Elaine
E
Campbell
Laura
L
Chambon
Pierre
P
Hardman
Matthew J
MJ
Ashcroft
Gillian S
GS
D000818:Animals; D002369:Castration; D004789:Enzyme Activation; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D007249:Inflammation / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D010052:Ovariectomy; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects*
D047628:Estrogen Receptor alpha; D061965:Matrix Metalloproteinase Inhibitors; D004958:Estradiol; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14
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