Original Article
Journal of Investigative Dermatology (2005) 124, 1149–1161; doi:10.1111/j.0022-202X.2005.23736.x
Topical Application of 17
-Estradiol Increases Extracellular Matrix Protein Synthesis by Stimulating TGF-
Signaling in Aged Human Skin In Vivo
Eui Dong Son*, Jin Young Lee*, Serah Lee†, Mi Sun Kim†, Byeong Gon Lee*, Ih Seoup Chang* and Jin Ho Chung†
- *Amorepacific Corp/R&D Center, Gyeonggi-do, Korea
- †Department of Dermatology, Seoul National University College of Medicine and Laboratory of Cutaneous Aging Research, Clinical Research Institute, Seoul National University Hospital, and Institute of Dermatological Science, Seoul National University, Seoul, Korea
Correspondence: Jin Ho Chung, MD, PhD, Department of Dermatology, Seoul National University Hospital 28, Yungon-dong, Chongno-Gu, Seoul 110-744, Korea. Email: jhchung@snu.ac.kr
Received 8 June 2004; Revised 14 January 2005; Accepted 30 January 2005; Published online 3 June 2005.
Abstract
To investigate the effects of topically applied 17
-estradiol on the expression of extracellular matrix proteins in aged human skin, 17
-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 17
-estradiol was found to increase the expression of type 1 procollagen mRNA and protein significantly in human aged skin in vivo. In addition, MMP-1 protein levels were reduced by topical 17
-estradiol. The expressions of TGF-
1, TGF-
type II receptor, and Sma and Mad related (Smad)3 were increased by topical 17
-estradiol in aged human skin, and TGF-
1 neutralizing antibody inhibited 17
-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 17
-estradiol. Topical 17
-estradiol also increased keratinocyte proliferation and the epidermal thickness in aged human skin. We also observed the same effects of topical 17
-estradiol in young skin. In conclusion, our results suggest that topical 17
-estradiol treatment may improve the cutaneous function of aged human skin by improving the connective tissue and increasing epidermal thickness.
Keywords:
17
-estradiol, extracellular matrix proteins, skin aging, Smad, TGF-
Abbreviations:
MMP, matrix metalloproteinases; PIC, anti-human procollagen type I C-peptide antibody; Smad, Sma and Mad related; SP1.D8, anti-procollagen type 1 amino-terminal extension peptide antibody; T
RI, TGF-
type I receptor; T
RII, TGF-
type II receptor
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