Pharmacological Characterization and Cellular Localization of Insulin-Like Growth Factor-I (IGF-I) Binding to Human Placenta during the Course of Pregnancy and at Term

Abstract 489 Poster Session I, Saturday, 5/1 (poster 291)

IGF-I and its receptor (IGF-IR) have been implicated in the regulation of fetal and placental growth and development. IGF-IR mRNA has been localized in all placental cell types, however, little is known about the pharmacology and in situ tissue localization of functional IGF-I binding sites in the human placenta. We describe IGF-I binding characteristics in cryosections of human placenta at 14, 24 and 40 weeks gestation and in situ localization of IGF-I binding sites by in situ autoradiography and immunocytochemistry. 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 IGF-I to specific binding sites between 14 and 24 weeks and similar affinity for the rest of pregnancy. 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. Quantitative autoradiography localized [¹²⁵I]IGF-I binding to decidua and trophoblast cells of chorionic villi, in the latter with a gradual shift from the cytotrohoblast (week 14, 24) to the syncytiotrophoblast (week 40). Furthermore, towards term enhanced [¹²⁵I]IGF-I binding occurred to fetal vessels in chorionic villi, the highest binding density was localized to the trophoblast of the stem and intermediate villi. Immunocytochemistry showed an identical pattern of IGF-IR localization to IGF-I binding obtained by autoradiography. In summary, our results indicate that [¹²⁵I]IGF-I binding occurs to cells that are responsible for placental growth in early pregnancy and for fetal growth during the second half of gestation. The strikingly high binding to the trophoblast -as a highly growth sensitive tissue-underlines the importance of the IGF-system in placental development.