Evidence of insulin-like growth factor binding protein-3 proteolysis during growth hormone stimulation testing

Benjamin U. Nwosu, University of Massachusetts Medical School
Leslie A. Soyka, University of Massachusetts Medical School
Amanda Angelescu, University of Massachusetts Medical School
Mary M. Lee, University of Massachusetts Medical School

Abstract

OBJECTIVES: The ternary complex is composed of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and acid labile subunit (ALS). Growth hormone (GH) promotes IGFBP-3 proteolysis to release free IGF-I, ALS, and IGFBP-3 fragments. Our aim was to determine whether elevated GH levels during GH stimulation testing would trigger IGFBP-3 proteolysis.

DESIGN: This prospective study of 10 short prepubertal children (height standard deviation score -2.37 +/- 0.31) used arginine and GH releasing hormone stimulation to study dynamic changes in the ternary complex moieties. IGFBP-3 was measured in two assays: a radioimmunoassay (RIA) that detects both cleaved and intact IGFBP-3; and an immunochemiluminescence assay (ICMA) that detects only intact IGFBP-3.

RESULTS: IGFBP-3 measured by RIA increased by 19% (p < 0.05), while IGFBP-3 measured by ICMA did not significantly increase (6.1%).

CONCLUSION: The significant increase in IGFBP-3 measured by RIA, but not ICMA, provides evidence of IGFBP-3 proteolysis during acute GH stimulation.