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Paracrine actions of IGF binding proteins
F Minuto1, A Barreca, P Del Monte
1Cattedre di Fisiopatologia Endocrina, Università di Genova, Italy.
Acta Endocrinologica
|January 1, 1991
Summary
Insulin-like growth factors (IGFs) may act locally (paracrine) rather than systemically (endocrine). Extrahepatic synthesis supports local actions, with binding proteins influencing IGF-I distribution to target cells like keratinocytes.
Area of Science:
- Endocrinology
- Cell Biology
- Molecular Biology
Background:
- Insulin-like growth factors (IGFs) are synthesized ubiquitously, suggesting a paracrine mode of action.
- High circulating concentrations of IGFs imply an endocrine function, with the liver producing most circulating IGF-I.
- Extrahepatic synthesis of IGFs supports local paracrine or autocrine actions.
Purpose of the Study:
- To investigate the dual endocrine and paracrine roles of IGFs.
- To elucidate the mechanisms of IGF-I transport and action.
- To understand the contribution of extrahepatic IGF synthesis.
Main Methods:
- Hypothesizing based on ubiquitous peptide synthesis and circulating concentrations.
- Analyzing the roles of liver and peripheral fibroblasts in IGF production.
- Examining IGF binding protein (IGFBP) interactions and their effects on IGF-I distribution.
Main Results:
- The liver produces IGF-I and IGFBP for circulation, with limited free IGF-I crossing capillary walls.
- Fibroblasts synthesize IGF peptides and IGFBP, while keratinocytes possess receptors but not synthesis capabilities.
- IGFBP-3, produced by fibroblasts, has a high affinity for IGF-I, influencing its binding and directing it to keratinocytes.
Conclusions:
- The findings support a significant paracrine role for IGFs, particularly in local tissue regulation.
- IGF binding proteins play a crucial role in modulating IGF action and targeting.
- Further research into IGF signaling in epithelial cells, including neoplastic ones, is warranted.