title: Differential effects of estradiol and raloxifene on collagen biosynthesis in cultured human skin fibroblasts.
abstract: The dose-dependent effect of a 24 h treatment with estradiol (E(2)) (1, 2, 5, 10 nM) and raloxifene (Rx) (1, 5, 10, 20 microM) on ER alpha and ER beta mRNA expression, collagen bio-synthesis, prolidase activity, MMP-2, MMP-9, insulin-like growth factor I receptor expression (IGF-1R) and beta1-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 microM concentrations had greater stimulative effect on collagen biosynthesis, prolidase activity and IGF-1R expression compared to E(2) at 2 and 5 nM concentration. Both studied ER ligands had no effect on beta1-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, transcriptional regulation of collagen genes by estrogen receptor-raloxifene complex, increasing of prolidase activity or finally by inhibition of MMP-9 expression.
authors.affiliation: Department of Medicinal Chemistry, Medical Academy of Bialystok, 15-230 Bialystok, Poland.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Surazynski
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Jarzabek
authors.forename: Jozef
authors.initials: J
authors.lastname: Haczynski
authors.forename: Piotr
authors.initials: P
authors.lastname: Laudanski
authors.forename: Jerzy
authors.initials: J
authors.lastname: Palka
authors.forename: Slawomir
authors.initials: S
authors.lastname: Wolczynski
mesh_terms: D000368:Aged; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D004150:Dipeptidases / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics; D012867:Skin / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D019012:Integrin beta1; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D003094:Collagen; D017526:Receptor, IGF Type 1; D004150:Dipeptidases; C022449:proline dipeptidase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9