Effects of 17beta-estradiol on matrix metalloproteinase-1 synthesis by human dermal fibroblasts.
BACKGROUND
Hormone replacement therapy (HRT) has been used in treatment of various menopausal disorders. It has been well documented that HRT increases the amount of dermal collagen and skin thickness in vivo. However little is known about the effects of female sex hormones on dermal fibroblasts in vitro.


OBJECTIVE
The aim of this study is to determine whether or not 17beta-estradiol affects mRNA expression and production of type I collagen, matrix metalloproteinases-1 (MMP-1), tissue inhibitor metalloproteinases-1 (TIMP-1) or transforming growth factor-beta1 (TGF-beta1) by human dermal fibroblasts.


METHODS
Fibroblasts were cultured with and without 17beta-estradiol for 6h. We evaluated the changes of mRNA expressions and protein production of type I collagen, MMP-1, TIMP-1 and TGF-beta1.


RESULTS
The mRNA expressions of collagen alpha1(I), MMP-1, TIMP-1, TGF-beta1 were not changed by 17beta-estradiol stimulations at a concentration of 10(-12) to 10(-8) M. However, 17beta-estradiol at concentrations of 10(-12) and 10(-10) M exhibited inhibitory effects on proMMP-1, but not type I collagen or TIMP-1 synthesis. The synthesis of TGF-beta1 by fibroblasts stimulated with 10(-8) M of estradiol was significantly increased as compared with the control. However, the level of TGF-beta type II receptor phosphorylation was not elevated under the same conditions.


CONCLUSIONS
Suppressed synthesis of MMP-1 at a low concentration of 17beta-estradiol may be partly involved in the dermal tissue remodeling to inhibit the degradative change.
Qu
LuDan
L
Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. quludan@med.gunma-u.ac.jp
Abe
Masatoshi
M
Yokoyama
Yoko
Y
Ishikawa
Osamu
O
D000328:Adult; D002478:Cells, Cultured; D024042:Collagen Type I / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D024042:Collagen Type I; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004958:Estradiol; D020781:Matrix Metalloproteinase 1