Secretion of insulin-like growth factor-I and binding proteins by rat liver fat-storing cells: regulatory role of platelet-derived growth factor

Endocrinology. 1990 Nov;127(5):2343-9. doi: 10.1210/endo-127-5-2343.


Insulin-like growth factor (IGF-I) is synthesized in multiple organs, including the liver, and may play a role in tissue growth and repair. We report that liver fat-storing cells (FSC) secrete IGF-I immunoreactivity in the culture medium. Secretion of IGF-I immunoreactivity was blocked in the presence of cycloheximide, suggesting de novo synthesis. Culture medium conditioned by FSC was concentrated and applied to a Sephadex G100 column equilibrated in a denaturing buffer. Two major species with apparent mol wts of 7.5 and greater than 25 k were identified by IGF-I RIA. Reverse phase HPLC of the 7.5 kilodalton species (the size of IGF-I) showed that it eluted in a single peak. To determine whether the higher mol wt species possessed IGF-I binding activity, appropriate fractions were desalted, incubated with [125I]IGF-I for 2 h at 30 C and applied to a Sephadex G100 column equilibrated in a nondissociating buffer. The major peak of radioactivity was confined to a high mol wt region. Western blot ligand analysis revealed the presence of two insulin-like growth factor binding proteins of approximately 28 and 31 kilodaltons. Platelet-derived growth factor, a potent mitogen for FSC, resulted in a 230% increase in release of IGF-I immunoreactivity that could be accounted for by an increase in IGF-I binding activity. In addition IGF-I increased DNA synthesis in FSC and this effect was additive to that of platelet-derived growth factor. IGF-I treatment also resulted in an increase in cell number. IGF-I and insulin-like growth factor binding proteins secreted by FSC may play a role in the hepatic tissue response to injury via autocrine and/or paracrine mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Carrier Proteins / metabolism*
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • DNA / biosynthesis
  • Immunologic Techniques
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I / metabolism*
  • Lipid Metabolism*
  • Liver / cytology
  • Liver / metabolism*
  • Male
  • Platelet-Derived Growth Factor / pharmacology
  • Platelet-Derived Growth Factor / physiology*
  • Rats
  • Rats, Inbred Strains
  • Somatomedins / metabolism
  • Thymidine / metabolism


  • Carrier Proteins
  • Insulin-Like Growth Factor Binding Proteins
  • Platelet-Derived Growth Factor
  • Somatomedins
  • Insulin-Like Growth Factor I
  • DNA
  • Thymidine