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Abstract
Insulin-like growth factor binding protein-3 (IGFBP-3) is known to modulate the actions of insulin-like growth factors (IGF)-I and -II at the level of the cell. Proposed mechanisms include association of IGFBP-3 with cell surface proteoglycan, with cell surface binding proteins, proteolysis and/or internalization of IGFBP-3. In previous studies we have characterized a protein of 40 kDa in extracts of ovine pancreas and muscle which binds IGFBP-3 on ligand blot analyses. This paper reports the identity of the pancreatic species as procarboxypeptidase A (peptidyl-l-amino acid hydrolase, E.C. 3.4.17.1; proCPA). Identity was established by amino terminal sequence analysis, binding studies with pure bovine carboxypeptidase A (CPA) and observations that the binding activity was present in pancreatic secretions consistent with the role of proCPA as a secretory zymogen. The binding activity was inhibited by unlabelled IGFBP-3 at high doses (10 μg/ml) and reduced but not abolished by preincubation of 125I-IGFBP-3 with excess IGF-I. Digestion of 125I-IGFBP-3 with mature CPA produced a 26 kDa product. Modification of IGFBP-3 by CPA or binding to proCPA may provide a mechanism for modulation of IGFBP activity and hence IGF action.
Journal of Endocrinology (1996) 150, 51–56
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ABSTRACT
The effect on young lambs of 0·25 mg recombinant bovine GH (bGH)/kg per day on plasma concentrations of insulin-like growth factor-I (IGF-I), glucose, specific hepatic GH binding and body composition changes was examined at two levels of nutrition (lucerne pellets; 3 and 1·7% of body weight/day). Lambs on low levels of nutrition had low plasma IGF-I (P < 0·001). Plasma concentrations of IGF-I were increased by bGH treatment at both levels of nutrition, with the high nutrition group showing the greatest IGF-I response after 3 and 40 days of bGH treatment. Plasma glucose, after 40 days, was higher overall (P < 0·05) in lambs on high nutrition. bGH treatment increased plasma glucose, with the response being greater in the well-fed lambs. Specific binding of GH to liver membranes was highest in lambs on high nutrition and on bGH treatment; no significant interaction between nutrition and bGH treatment was detected, indicating that specific binding of GH was increased proportionally by bGH at both nutritional levels. The major change in body composition was the reduced level of fatness in lambs treated with bGH. There was no significant effect of bGH on body weight although bGH treatment tended to increase weight gain of well-fed lambs and decreased weight loss of poorly nourished lambs.
The results show that, although there was a significant (P < 0·05) bGH/nutrition interaction for IGF-I there was no such interaction for body weight/components or specific GH binding to the liver. The results indicate that an increase in plasma IGF-I does not necessarily result in increases in growth or changes in carcass composition.
Journal of Endocrinology (1991) 128, 181–186