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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 Proteolysis¹

Medical Research Laboratories, Institute of Experimental Clinical Research, Aarhus University (C.S., J.F., H.Ø., N.M., A.F.), and the Surgical Research Unit, Department of Surgery L, University Hospital of Aarhus (P.K.-N., M.B.J., S.L.), DK-8000 Aarhus C, Denmark

Address all correspondence and requests for reprints to: Dr. Christian Skjærbæk, Medical Research Laboratories, Aarhus Kommune Hospital, Building 3, DK-8000 Aarhus C, Denmark. E-mail: cs{at}afdm.aau.dk

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 diminished affinity of the IGFBP-3 fragments for IGFs. We have investigated 18 patients undergoing elective ileo-anal J-pouch surgery. Patients were 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-II were measured by ultrafiltration of serum, and IGFBP-3 proteolytic activity was determined by a [¹²⁵I]recombinant human IGFBP-3 degradation assay. In the GH-treated group, total IGF-I increased preoperatively 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% preoperatively 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 relate to augmented IGFBP-3 proteolysis.

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