Enzymatic conversion of IGF-I to des(1-3)IGF-I in rat serum and tissues: a further potential site of growth hormone regulation of IGF-I action.
We recently identified and characterized a protease present in rat serum which is capable of generating des(1-3)IGF-I. In this study, we have investigated the effects of GH deficiency and replacement on the activity of this protease in rat serum and tissue extracts. Protease activity was significantly higher in sera from hypophysectomized (hypox) rats than sham-operated rats (P < 0.001) and GH treatment of hypox rats (human GH, 100 micrograms/100 g body weight i.p. for 10 days) significantly reduced the levels towards normal. The addition of IGF-I to hypox rat serum to achieve IGF-I concentrations comparable with or greater than that seen in normal rat serum had no effect on the measured protease activity. Protease activity was also detected in tissue extracts. The level of protease activity in the various tissues from sham-operated rats demonstrated the following order: liver > testes > heart > skeletal muscle > lung > thymus > kidney > brain > spleen. In all tissue extracts examined, except that from the lung, the levels of protease activity were higher in extracts from hypox rats compared with sham-operated rats. The largest differences between tissue extracts from hypox and sham-operated rats were seen in spleen (4-fold higher), kidney (2.27-fold), testes (1.55-fold) and heart (1.31-fold). In the liver, kidney and testes, GH treatment significantly reduced protease activity. Since the pattern of serum IGF-binding proteins (IGFBPs) differ in hypox rats compared with normal rats, we determined whether these changes could result in enhanced serum binding of des(1-3)IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)
Yamamoto
H
H
Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.
Murphy
L J
LJ
D000818:Animals; D001681:Biological Assay; D010450:Endopeptidases / Q000097:blood / Q000378:metabolism*; D013006:Growth Hormone / Q000172:deficiency / Q000378:metabolism*; D007016:Hypophysectomy; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000201:enzymology; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000201:enzymology; D013737:Testis / Q000201:enzymology
D018972:Insulin-Like Growth Factor Binding Protein 3; D010446:Peptide Fragments; C058957:insulin-like growth factor 1, des-(1-3)-; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D010450:Endopeptidases