Insulin-like growth factor I binding in hepatocytes from human liver, human hepatoma, and normal, regenerating, and fetal rat liver.

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