Mol. Hum. Reprod. Advance Access published online on June 26, 2008
Molecular Human Reproduction, doi:10.1093/molehr/gan038
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Insulin-like Growth Factor Binding Protein-1 (IGFBP-1) Induces Decidualization of Human Endometrial Stromal Cells via 
5β1 Integrin
Department of Obstetrics and Gynecology, Kyorin University School of Medicine 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan
Address Correspondence to: Keiji Sakai, MD, PhD Department of Obstetrics and Gynecology Kyorin University School of Medicine 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan +81 (422) 47-5511 phone +81 (422) 47-3177 fax E-mail: sakaik{at}aol.com
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 (E2) and/or medroxy progesterone acetate (MPA) in the presence or the absence of IGFBP-1 and, LR3-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 analyzed using a biosensor.
MPA and E2 induced decidualization of stromal cells, while LR3-IGF-I inhibited decidualization by MPA and E2 as well as PRL and IGFBP-1 secretion into medium. IGFBP-1 induced decidualization of stromal cells in the absence of MPA and E2 in the medium. IGFBP-1-induced decidualization was not inhibited by the addition of LR3IGF-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-
5β1 integrin antibody inhibited its binding.
These results suggest that IGFBP-1 produced by endometrium can mediate progesterone-induced decidualization possibly by interacting with 5β1 integrin on the surface of endometrial stromal cells.
Key Words: IGFBP-1/decidualization/endometrium/integrin/human stromal cells
Submitted on October 26, 2007; resubmitted on June 2, 2008; accepted on June 20, 2008.