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 profi le of insulin-like growth factor-binding proteins secreted by human fe tal tissues and their immunologic identification and tissue-specific g ene expression. STUDY DESIGN: Explants of midgestational fetal tissues from seven fetuses were cultured with and without cycloheximide. Cond itioned media were examined for insulin-like growth factor-binding pro teins by Western ligand blot analysis, and insulin-like growth factor- binding proteins were identified by immunoprecipitation. Gene expressi on was analyzed by Northern analysis. RESULTS: Fetal liver and kidney explants secreted insulin-like growth factor-binding protein-1 to insu lin-like growth factor-binding protein-4, with insulin-like growth fac tor-binding protein-1 being the most prominent in liver. Fetal lung se creted insulin-like growth factor-binding protein-2 and insulin-like g rowth factor-binding protein-4 and lesser amounts of insulin-like grow th factor-binding protein-3, whereas white matter explants secreted ex clusively insulin-like growth factor-binding protein-2 and insulin-lik e growth factor-binding protein-4. Cycloheximide inhibited secretion o f binding proteins, suggesting de novo synthesis. Northern blot analys es were consistent with the protein studies. CONCLUSION: These data de monstrate that insulin-like growth factor-binding protein secretion by fetal tissues is tissue specific.