title: Topical application of 17beta-estradiol increases extracellular matrix protein synthesis by stimulating tgf-Beta signaling in aged human skin in vivo.
abstract: 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.
authors.affiliation: Amorepacific Corp/R&D Center, Gyeonggi-do, Korea.
authors.forename: Eui Dong
authors.initials: ED
authors.lastname: Son
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Serah
authors.initials: S
authors.lastname: Lee
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Byeong Gon
authors.initials: BG
authors.lastname: Lee
authors.forename: Ih Seoup
authors.initials: IS
authors.lastname: Chang
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Chung
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage* / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015595:Skin Aging / Q000502:physiology*; D051900:Smad3 Protein; D051906:Smad7 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014333:Tropoelastin / Q000235:genetics / Q000378:metabolism; D054392:Adipokines
chemical_list: D000906:Antibodies; D024042:Collagen Type I; D004268:DNA-Binding Proteins; D004958:Estradiol; D016326:Extracellular Matrix Proteins; D000071838:Fibrillin-1; D000071837:Fibrillins; D020781:Matrix Metalloproteinase 1; D008840:Microfilament Proteins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; D051900:Smad3 Protein; D051906:Smad7 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014333:Tropoelastin; C000605722:FBN1 protein, human; D054392:Adipokines; C497790:SMAD3 protein, human; C497806:SMAD7 protein, human; C508960:TGFB1 protein, human