Co-Authors:
Kachra, Z., Protein and Polypeptide Hormone Laboratory, Montreal, QC, Canada
Barash, I., Protein and Polypeptide Hormone Laboratory, Montreal, QC, Canada
Yannopoulos, C., Protein and Polypeptide Hormone Laboratory, Montreal, QC, Canada
N. Khan, M., Protein and Polypeptide Hormone Laboratory, Montreal, QC, Canada
Guyda, H.J., Departments of Medicine and Pediatrics, McGill University, Montreal, QC, Canada
Posner, B.I., Protein and Polypeptide Hormone Laboratory, Montreal, QC, Canada
Abstract:
The liver is a major site of production of insulinlike growth factor-I (IGF-I) and IGF binding proteins (IGF- BPs). GH decisively influences IGF-I production. To study the role of GH and glucagon in the regulation of IGF-I and IGF-BP production, we examined IGF-I and IGF-BPs secreted by primary rat hepatocytes cultured in a serum-free medium. Glucagon (1 X 10-8m) stimulated IGF-I secretion and IGF-BP secretion. Bovine GH (bGH, 300 ng/ml) stimulated IGF-I secretion but suppressed IGF-BP secretion. Combining bGH and glucagon significantly augmented IGF-I secretion above the level seen with each individual agent. The inhibitory effect of bGH on IGF-BP secretion was reversed by glucagon. The major species of IGF-BPs secreted by hepatocytes were found, on Western ligand blotting, to be 24K and 30-34K. All species of secreted IGF-BPs appeared to be comparably affected by glucagon, bGH, and their combination. Northern analysis of IGF-I mRNA revealed three transcripts of 0.7-1.1 kilobases (kb), 1.8 kb, and 7.0 kb. Glucagon stimulated IGF-I mRNA levels 1.8- to 2.0-fold, whereas bGH stimulated IGF-I mRNA levels 2.0- to 2.5-fold. When hepatocytes were incubated with glucagon and bGH for 6 h, IGF-I mRNA levels were augmented 10-fold. Glucagon, in the presence of 50 ng/ml bGH, had a dose-dependent effecton IGF-I mRNA accumulation from a 6-fold level of stimulation at 50 ng/ml of glucagon to a 9-fold level of stimulation at 1000 ng/mlglucagon. This study has demonstrated that glucagon, as well as GH, has significant effects on the production of both IGF-I and IGF- BPs. Of particular interest was the marked augmentation of hepatic IGF-I messenger RNA levels and the reversal of the low levels of IGF-BP production seen on adding glucagon to bGH. © 1991 by The Endocrine Society.