Synthesis and secretion of insulin-like growth factor and its binding protein by the perfused rat liver: dependence on growth hormone status.
Isolated livers of normal and hypophysectomized (hypox) rats with or without GH replacement therapy were perfused in an erythrocyte-free recirculating perfusion system for 4 h in the presence of [35S]cysteine. Albumin secretion and synthesis increased in a parallel and linear fashion over 4 h. The albumin secretion rates were 0.53 and 0.21 mg/g liver h-1 in normal and hypox animals, respectively. Insulin-like growth factor (IGF) secretion, measured as insulin equivalents in the fat cell assay as well as in a competitive protein binding assay, and IGF synthesis, as determined from [35S]cysteine incorporation into immunoprecipitable IGF, likewise increased linearly and in parallel throughout the perfusion time. The IGF secretion rate was 50 microU/g liver h-1. The secreted IGF had a molecular weight of approximately 7700 daltons. Secretion and synthesis of IGF were reduced to 11% in hypox rats and were largely restored by human GH replacement therapy (to 86% of normal). A single specific binding protein with an approximate molecular weight of 35,000 was detected in the perfusate. The binding protein was measured by covalent cross-linkage to [125I]IGF I by dimethylsuberimidate. The secretion of this binding protein was 62% of normal in hypox animals and 79% in GH-treated hypox rats. The data suggest that IGF is continuously synthesized and released by the liver. Assuming a half-life for IGF of 3 h in the normal rat, a plasma volume of 8 ml, and a liver weight of 8.5 g, the rate of IGF production by the perfused normal rat liver (50 microU/g liver h-1) would be sufficient to maintain serum IGF at the concentration determined in normal rat serum (approximately 130 microU/ml). This suggests that the liver is the major site of IGF production in the rat.
D000418:Albumins / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D013006:Growth Hormone / Q000494:pharmacology*; D007016:Hypophysectomy; D007328:Insulin / Q000096:biosynthesis*; D018969:Insulin-Like Growth Factor Binding Proteins; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size; D010452:Peptide Biosynthesis; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013002:Somatomedins / Q000096:biosynthesis*
D000418:Albumins; D002352:Carrier Proteins; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D013006:Growth Hormone