Topical Application of 17β-Estradiol Increases Extracellular Matrix Protein Synthesis by Stimulating TGF-β Signaling in Aged Human Skin In Vivo

To investigate the effects of topically applied 17β-estradiol on the expression of extracellular matrix proteins in aged human skin, 17β-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 17β-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 17β-estradiol. The expressions of TGF-β1, TGF-β type II receptor, and Sma and Mad related (Smad)3 were increased by topical 17 β-estradiol in aged human skin, and TGF-β1 neutralizing antibody inhibited 17β-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 17β-estradiol. Topical 17β-estradiol also increased keratinocyte proliferation and the epidermal thickness in aged human skin. We also observed the same effects of topical 17β-estradiol in young skin. In conclusion, our results suggest that topical 17β-estradiol treatment may improve the cutaneous function of aged human skin by improving the connective tissue and increasing epidermal thickness.