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J. Biochem, 1988, Vol. 103, No. 4 700-706
© 1988 Japanese Biochemical Society

research-article

Autocrine Mechanism of Growth of Neonatal Rat Hepatocytes in Primary Culture1

Toshikazu Nakamura, Takeru Fujii2 and Akira Ichihara3

Institute for Enzyme Research, University of Tokushima Tokushima, Tokushima 770

3To whom correspondence should be addressed.

Hepatocytes from neonatal rats of 0 to 3 days old grew actively in primary culture without added serum or growth factors. In these culture conditions, growth of hepatocytes decreased progressively with increase in age of the rats from which they were isolated, and hepatocytes from rats of 2 weeks old showed scarcely any growth. Actively growing hepatocytes were found to secrete a growth factor that promoted their growth and that of Swiss 3T3 cells, but not that of adult hepatocytes. This growth factor in conditioned medium of growing hepatocytes was heat- and acid-stable, but sensitive to trypsin, and had a molecular weight of over 10,000. It did not inhibit the binding of [125I] epidermal growth factor to its receptor, and its growth promoting activity was not inhibited by monoclonal antibody against insulin-like growth factor II. Therefore, it seems to be a new growth factor. These results, together with previous findings (Nakamura, T., Nagao, M., & Ichihara, A. (1987) Exp. Cell Res. 169, 1–14) demonstrated a reciprocal relation between growth and maturation of neonatal hepatocytes during development, like that of adult cells, but indicated that unlike growth of the latter, growth of neonatal cells is induced by an autocrine mechanism.

1This work was supported by research grants from the Ministry of Education, Science and Culture of Japan and the Uehara Foundation, Tokyo.

2Present address: Research Laboratories, Teikoku Pharmaceutical Co., Kagawa.


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