The dose-dependent effect of a 24 h treatment with estradiol (E2) (1, 2, 5, 10 nM) and raloxifene (Rx) (1, 5, 10, 20 μM) on ERα and ERβ mRNA expression, collagen bio-synthesis, prolidase activity, MMP-2, MMP-9, insulin-like growth factor I receptor expression (IGF-1R) and β1-integrin expressions in cultured fibroblasts obtained from postmenopausal women were examined. Both ligands increased mRNA expression of ER compared to control. Rx at 5 and 10 μM concentrations had greater stimulative effect on collagen biosynthesis, prolidase activity and IGF-1R expression compared to E2 at 2 and 5 nM concentration. Both studied ER ligands had no effect on β1-integrin receptor expressions. MMP-2 expression was not detected in human skin fibroblast culture. In contrast to estradiol raloxifene inhibited the expression of MMP-9. Raloxifene had stronger positive stimulative effects on collagen biosynthesis, through different biochemical mechanisms, than estradiol in human skin fibroblasts and might reverse some of the postmenopausal changes in skin or connective tissue. Increase of collagen synthesis induced by raloxifene may be activated by both estrogen receptor dependent and independent pathways such as up-regulation of estrogen receptors, up-regulation of IGF receptor, trans-criptional regulation of collagen genes by estrogen receptor-raloxifene complex, increasing of prolidase activity or finally by inhibition of MMP-9 expression.

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