title: Metformin modulates IL-8, IL-1β, ICAM and IGFBP-1 expression in human endometrial stromal cells.
abstract: To evaluate the effects of metformin on endometrial stromal cell gene expression and on the decidualization process, endometrial biopsies were collected from five healthy, regularly cycling women. Stromal cell culture was performed and decidualized with oestrogen/progesterone in the presence or absence of metformin and thereafter stimulated with insulin. The effect of metformin on decidualization was analysed by prolactin determination in the cell culture supernatant. Gene expression of insulin-like growth factor binding protein 1 (IGFBP-1), interleukin (IL) 8 and 1β and intercellular adhesion molecule (ICAM) was analysed by real-time PCR. Decidualization was significantly diminished in cells incubated with metformin (P<0.05) accompanied by a significant reduction of prolactin secretion in the supernatant (day 10: 2.2 fold, P<0.05; day 15: 3.1 fold, P<0.05). IGFBP-1 gene expression was reduced after long-term metformin exposure (7.7 fold, P<0.05). The negative effect of insulin on IL-8 (4.8 fold) and IL-1β (9.3 fold) gene expression was similarly found in cells incubated with metformin. As far as is known, this is the first demonstration of a change in endometrial gene and protein expression after in-vitro stimulation with metformin, including a diminished decidualization process and changes in genes relevant to implantation.
authors.affiliation: Department of Gynecological Endocrinology and Reproductive Medicine, Ruprecht-Karls-University, Heidelberg, Germany. ariane.germeyer@med.uni-heidelberg.de
authors.forename: Ariane
authors.initials: A
authors.lastname: Germeyer
authors.forename: Julia
authors.initials: J
authors.lastname: Jauckus
authors.forename: Markus
authors.initials: M
authors.lastname: Zorn
authors.forename: Bettina
authors.initials: B
authors.lastname: Toth
authors.forename: Edison
authors.initials: E
authors.lastname: Capp
authors.forename: Thomas
authors.initials: T
authors.lastname: Strowitzki
mesh_terms: D004717:Endometrium / Q000166:cytology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D012739:Gonadal Steroid Hormones; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008687:Metformin / Q000494:pharmacology*; D011388:Prolactin / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D012739:Gonadal Steroid Hormones; C032231:IGFBP1 protein, human; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D053583:Interleukin-1beta; D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1; D011388:Prolactin; D008687:Metformin