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Expression and the Biological Activities of Insulin-Like Growth Factor-Binding Protein Related Protein 1 in Rat Uterus during the Periimplantation Period

Department of Endocrine Pharmacology (K.T., M.K., M.Ya., M.Yo., H.K.), Tokyo University of Pharmacy and Life Science, Tokyo 192-0392, Japan; and Department of Tumor Biochemistry (T.H., K.I.), The Tokyo Metropolitan Institute of Medical Science, Tokyo 113-0032, Japan

Address all correspondence and requests for reprints to: Kazuhiro Tamura or Hiroshi Kogo, Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1, Hachioji-shi 192-0392, Japan. E-mail: hiro{at}ps.toyaku.ac.jp; or kogo{at}ps.toyaku.ac.jp.

IGF binding protein-related protein 1 (IGFBP-rP1) is highly expressed in the rat uterus around the time of implantation. In the present study, we determined the periimplantation localization of IGFBP-rP1 mRNA and assessed the effects of recombinant IGFBP-rP1 on the proliferative and prostacyclin (PGI₂)-producing abilities of cultured endometrial cells early in pregnancy. IGFBP-rP1 mRNA was detected at high levels in endometrial stromal cells close to the smooth muscle of interimplantation sites around the time of implantation but absent from decidual zones surrounding the embryo. Differential uterine IGFBP-rP1 expression was also recognized in the delayed implanting pregnant model, but the level of mRNA decreased as decidual tissues formed in the decidualization model. Recombinant IGFBP-rP1 inhibited the proliferation of endometrial stromal cells in vitro and arrested them in the G₁ phase of the cell cycle. Furthermore, IGFBP-rP1 significantly stimulated PGI₂ synthesis and cyclooxygenase II mRNA expression in myometrial cells, both of which are essential molecules for successful implantation. These data suggest that IGFBP-rP1 is an implantation-associated protein and that it modulates the proliferation of rat uterine cells and their production of PGI₂ during the periimplantation period.

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