Abstract 35

Background: IGF-I and its receptor (IGF-IR) have been implicated in the regulation of fetal growth, however, little is known about the pharmacology and in situ localization of functional IGF-I binding sites in the placenta. Methods: We describe IGF-I binding characteristics in human placenta at 14, 24 and 40 weeks gestation and in situ localization of IGF-I binding sites by autoradiography and immunocytochemistry. Results: Binding of [125I]IGF-I to placental cryosections was specific and halfmaximally inhibited by 7.9 ± 0.4, 1.1 ± 0.2 and 0.9 ± 0.2 × 10-9 M IGF-I at 14, 24 and 40 weeks gestation, respectively, demonstrating an increase in affinity of binding sites between 14 and 24 weeks and similar affinity later. Des(1-3) IGF-I inhibited binding of [125I]IGF-I at 4.5 ± 0.7, 0.5 ± 0.1 and 0.2 ± 0.1 × 10-9 M IGF-I indicating that this binding occurred to a smaller portion of specific IGF-IR and IGFBP-3 and a larger portion of different IGF-I binding species. Autoradiography localized [125I]IGF-I binding to decidua and trophoblast cells, in the latter with a shift from the cytotrohoblast (week 14) to the syncytiotrophoblast (week 40). Towards term enhanced [125I]IGF-I binding occurred to fetal vessels, the highest binding density was localized to trophoblast of the stem/intermediate villi. Immunocytochemistry showed an identical pattern of IGF-IR localization. Conclusions: Our results indicate that [125I]IGF-I binds to cells that are responsible for placental growth in early pregnancy and for fetal growth during later gestation. The high binding to trophoblast underlines the importance of the IGF-system in placental development.