INSULIN-LIKE GROWTH FACTOR-BINDING PROTEINS IN THE HUMAN FETUS - TISSUE-SPECIFIC PROTEIN SECRETION, IMMUNOLOGICAL CHARACTERIZATION, AND GENE-EXPRESSION

OBJECTIVES: The objectives of this study were to investigate the profile of insulin-like growth factor-binding proteins secreted by human fetal tissues and their immunologic identification and tissue-specific gene expression. STUDY DESIGN: Explants of midgestational fetal tissues from seven fetuses were cultured with and without cycloheximide. Conditioned media were examined for insulin-like growth factor-binding proteins by Western ligand blot analysis, and insulin-like growth factor-binding proteins were identified by immunoprecipitation. Gene expression was analyzed by Northern analysis. RESULTS: Fetal liver and kidney explants secreted insulin-like growth factor-binding protein-1 to insulin-like growth factor-binding protein-4, with insulin-like growth factor-binding protein-1 being the most prominent in liver. Fetal lung secreted insulin-like growth factor-binding protein-2 and insulin-like growth factor-binding protein-4 and lesser amounts of insulin-like growth factor-binding protein-3, whereas white matter explants secreted exclusively insulin-like growth factor-binding protein-2 and insulin-like growth factor-binding protein-4. Cycloheximide inhibited secretion of binding proteins, suggesting de novo synthesis. Northern blot analyses were consistent with the protein studies. CONCLUSION: These data demonstrate that insulin-like growth factor-binding protein secretion by fetal tissues is tissue specific.