DIFFERENTIAL CHANGES IN FREE AND TOTAL INSULIN-LIKE-GROWTH-FACTOR-I AFTER MAJOR, ELECTIVE ABDOMINAL-SURGERY - THE POSSIBLE ROLE OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-3 PROTEOLYSIS

Major surgery is accompanied by extensive proteolysis of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3). Proteolysis of IGFBP- 3 is generally believed to increase IGF bioavailability due to a dimin ished affinity of the IGFBP-3 fragments for IGFs. We have investigated 18 patients undergoing elective ileo-anal J-pouch surgery. Patients w ere randomized to treatment with GH (12 IU/day; n = 9) or placebo (n = 9) from 2 days before to 7 days after operation. Free IGF-I and IGF-I I were measured by ultrafiltration of serum, and IGFBP-3 proteolytic a ctivity was determined by a [I-125]recombinant human IGFBP-3 degradati on assay. In the GH-treated group, total IGF-I increased preoperativel y by 99%. Postoperatively, total IGF-I decreased by 48% (placebo) and 52% (GH). Immunoassayable IGFBP-3 decreased by 27% (placebo) and 26% ( GH). In the placebo-treated group, free IGF-I was unchanged throughout the study. In the GH-treated group, free IGF-I increased by 277% preo peratively and remained elevated after operation. IGFBP-3 proteolytic activity increased by 63-73% after operation. The relative elevations of free IGF-I levels despite decreased total IGF-I levels could thus r elate to augmented IGFBP-3 proteolysis.