Effect of epidermal growth factor on insulin-like growth factor-I (IGF-I) and IGF-binding protein synthesis by adult rat hepatocytes.
Growth hormone has been established as a primary regulator of IGF-I gene expression in adults, not only in liver but also in many extrahepatic tissues. We considered the possibility that IGF-I production by adult rat liver could also be stimulated by epidermal growth factor (EGF), a peptide known to be involved in liver regeneration. Chromatographic analysis performed after acid treatment of conditioned media revealed the presence of both immunoreactive (IR) IGF-I and IGF binding protein (IGFBP). Both IR IGF-I and IGFBP were present in the conditioned medium of adult rat hepatocytes in basal conditions. The stimulation of IGF-I and IGFBP secretion by EGF appears to be dose-dependent with a significant increment already evident at 5 nM. That EGF stimulates secretion is supported by the finding that IGF-I and IGFBP-1 mRNA levels are increased after EGF supplementation. We conclude that adult rat hepatocytes spontaneously produce IGF-I and IGFBP, and that EGF is able to increase their synthesis and secretion. This non-growth hormone-dependent regulation of IGF-I and IGFBP-1 production by adult rat hepatocytes in culture indicates an important autocrine/paracrine role for IGF-I, particularly during liver regeneration after extensive organ mass loss.
Barreca
A
A
Cattedra di Endocrinologia, DiSEM, University of Genova, Genua, Italy.
Voci
A
A
Minuto
F
F
de Marchis
M
M
Cecchelli
E
E
Fugassa
E
E
Giordano
G
G
Gallo
G
G
D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D066298:In Vitro Techniques; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000494:pharmacology; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D012313:RNA / Q000032:analysis; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine / Q000378:metabolism
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D004815:Epidermal Growth Factor; D012313:RNA; D007334:Insulin-Like Growth Factor I; D007930:Leucine; D013936:Thymidine