title: Insulin-like growth factor binding protein-1 induces decidualization of human endometrial stromal cells via alpha5beta1 integrin.
abstract: Progesterone is known to induce decidualization of human endometrial stromal cells in vitro. Decidualized stromal cells produce insulin-like growth factor binding protein-1 (IGFBP-1) as well as prolactin (PRL). In this study, we tested the possibility that IGFBP-1 directly stimulates endometrial stromal cell decidualization. Endometrial stromal cells were obtained from normal menstruating patients with uterine myoma at hysterectomy. Stromal cells were cultured for up to 4 weeks with estradiol (E(2)) and/or medroxy progesterone acetate (MPA) in the presence or the absence of IGFBP-1 and, LR(3)-IGF-I (an IGF-I analogue) that binds to the IGF-I receptor but has reduced affinity for IGFBPs. Decidualization of endometrial stromal cells was evaluated by morphological changes and PRL release into culture media. The binding of IGFBP-1 to endometrial cells was analysed using a biosensor. MPA and E(2) induced decidualization of stromal cells, while LR(3)-IGF-I inhibited decidualization by MPA and E(2) as well as PRL and IGFBP-1 secretion into medium. IGFBP-1 induced decidualization of stromal cells in the absence of MPA and E(2) in the medium. IGFBP-1-induced decidualization was not inhibited by the addition of LR(3)IGF-1 but was inhibited by the addition of an RGD peptide, however, the RGD peptide had no effect on decidualization when added alone. The binding analysis showed that IGFBP-1 bound to the surface of endometrial stromal cells and an anti-alpha5beta1 integrin antibody inhibited its binding. These results suggest that IGFBP-1 produced by endometrium can mediate progesterone-induced decidualization possibly by interacting with alpha5beta1 integrin on the surface of endometrial stromal cells.
authors.affiliation: Department of Obstetrics and Gynecology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Keiji
authors.initials: K
authors.lastname: Sakai
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Iwashita
mesh_terms: D002478:Cells, Cultured; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000494:pharmacology*; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D013002:Somatomedins / Q000494:pharmacology; D013256:Steroids / Q000494:pharmacology; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D039081:Integrin alpha5beta1; D013002:Somatomedins; D013256:Steroids; D004958:Estradiol; D011388:Prolactin; D017258:Medroxyprogesterone Acetate