Insulin-like growth factor I binding in hepatocytes from human liver, human hepatoma, and normal, regenerating, and fetal rat liver.
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Date
1988-04
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Authors
Caro, Jose F.
Poulos, John
Ittoop, Olivia
Pories, Walter J.
Flickinger, Edward G.
Sinha, Madhur K.
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Volume Title
Publisher
East Carolina University
Abstract
Insulin-like growth factor-I (IGF-I) in human hepatoma cells
(HEP-G2) has, in addition to its effect on cell growth, shortterm
metabolic effects acting through its own receptor. We
have demonstrated that normal human hepatocytes, compared
with HEP-G2 cells, have virtually no IGF-I binding sites. Because
the rate of growth is the major difference between the
hepatoma and the normal liver, we asked if normal liver might
express IGF-I binding sites under physiologic growth conditions.
Indeed, whereas adult rat hepatocytes have low IGF-I
binding sites similar to those in human liver, hepatocytes from
regenerating liver after 3 d subtotal hepatectomy have an approximately
sixfold increase (P < 0.005) and those from fetal
rat liver a - 12-fold increase (P < 0.005), to levels comparable
to those in the HEP-G2 cells. The specificity of 125I IGF-I
binding to its receptor was demonstrated by competition studies
with monoclonal antibodies directed toward the IGF-I and
the insulin receptors, with unlabeled IGF-I and insulin and by
affinity labeling experiments. Thus, if IGF-I has any shortterm
metabolic functions in the adult human liver, it is not
through interaction with its own receptor. Autocrine regulation
by IGF-I of liver growth appears possible since IGF-I binding
sites are expressed under pathological and physiological conditions
of growth. The mechanism that couples these two phenomena
remains to be elucidated. Originally published Journal of Clinical Investigation, Vol. 81, No. 4, Apr 1988
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Citation
Journal of Clinical Investigation; 81:4 p. 976-981
DOI
10.1172/JCI113451