Topical application of 17beta-estradiol increases extracellular matrix protein synthesis by stimulating TGF-Beta signaling in aged human skin in vivo

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Son, Eui Dong; Lee, Jin Young; Lee, Serah; Kim, Mi Sun; Lee, Byeong Gon; Chang, Ih Seoup; Chung, Jin Ho
Issue Date
Nature Publishing Group
J Invest Dermatol. 2005 Jun;124(6):1149-61.
Administration, TopicalAdultAgedAged, 80 and overAntibodies/pharmacologyCell Proliferation/drug effectsCollagen Type I/antagonists & inhibitors/genetics/metabolismDNA-Binding Proteins/genetics/metabolismEstradiol/*administration & dosage/pharmacologyExtracellular Matrix Proteins/*biosynthesisFemaleHumansKeratinocytes/cytologyMaleMatrix Metalloproteinase 1/metabolismMicrofilament Proteins/genetics/metabolismMiddle AgedProtein-Serine-Threonine KinasesRNA, Messenger/metabolismReceptors, Transforming Growth Factor beta/metabolismSignal Transduction/*physiologySkin Aging/*physiologySmad3 ProteinSmad7 ProteinTrans-Activators/genetics/metabolismTransforming Growth Factor beta/genetics/immunology/*metabolismTransforming Growth Factor beta1Tropoelastin/genetics/metabolism
To investigate the effects of topically applied 17beta-estradiol on the expression of extracellular matrix proteins in aged human skin, 17beta-estradiol (0.01%) and its vehicle (70% propylene glycol, 30% ethanol) were applied to aged (68-82 y, eight females and five males) human buttock skin under occlusion for 2 wk (three times per week). Topical 17beta-estradiol was found to increase the expression of type 1 procollagen mRNA and protein significantly in human aged skin in vivo. In addition, metalloproteinase (MMP-1 protein levels were reduced by topical 17beta-estradiol. The expressions of TGF-beta1, TGF-beta type II receptor, and Sma and Mad related (Smad)3 were increased by topical 17 beta-estradiol in aged human skin, and TGF-beta1 neutralizing antibody inhibited 17beta-estradiol-induced procollagen synthesis in cultured fibroblasts. We also found that the expressions of tropoelastin and fibrillin-1 mRNA and protein, and elastic fibers in aged skin were also increased by topical 17beta-estradiol. Topical 17beta-estradiol also increased keratinocyte proliferation and the epidermal thickness in aged human skin. We also observed the same effects of topical 17beta-estradiol in young skin. In conclusion, our results suggest that topical 17beta-estradiol treatment may improve the cutaneous function of aged human skin by improving the connective tissue and increasing epidermal thickness.
0022-202X (Print)
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College of Medicine/School of Medicine (의과대학/대학원)Dermatology (피부과학전공)Journal Papers (저널논문_피부과학전공)
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