Effects of 17beta-estradiol on matrix metalloproteinase-1 synthesis by human dermal fibroblasts

Abstract

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.

Conclusion: 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.