Cellular localization and hormonal regulation of biosynthesis of insulin-like growth factor binding proteins and of the acid-labile subunit within rat liver.
In the circulation, most of the IGFs are bound to a high molecular weight binding protein complex of 150 kDa that consists of IGF-I (or IGF-II), IGFBP-3 and the acid-labile subunit (ALS). Within rat liver, individual components of the 150 kDa complex are synthesized in different cellular compartments. ALS expression is localized in hepatocytes, but not in non-parenchymal cells. IGFBP-3 mRNA, however, is exclusively expressed in non-parenchymal and among them in endothelial and Kupffer cells. Co-cultures of hepatocytes and Kupffer cells were used as a model to study the hormonal regulation of biosynthesis of the components of the 150 kDa complex. Although expressed in different liver cell populations IGFBP-3 and ALS were regulated synergistically. Insulin stimulated both the expression of ALS and IGFBP-3 in co-cultures in a dose-dependent manner, while expression of IGFBP-I was decreased. Regulation of IGFBP-3 synthesis of Kupffer cells required a mediator that is secreted by hepatocytes, since IGFBP-3 expression in cultures of pure Kupffer cells did not respond to the stimulating effect of insulin.
Scharf
J G
JG
Department of Medicine, Georg-August-Universität, Göttingen, Germany.
Ramadori
G
G
Braulke
T
T
Hartmann
H
H
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D006023:Glycoproteins / Q000096:biosynthesis*; D007328:Insulin / Q000502:physiology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D008954:Models, Biological; D051381:Rats; D013002:Somatomedins / Q000378:metabolism*; D014018:Tissue Distribution
D002352:Carrier Proteins; D006023:Glycoproteins; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D013002:Somatomedins; C075944:insulin-like growth factor binding protein, acid labile subunit