Potentiation of hepatocyte sensitivity to mitogens by glutamic acid in primary culture

K. Hasegawa, Y. Miyata, B. I. Carr

Research output: Contribution to journalArticlepeer-review


Adult rat hepatocytes in primary culture responded to epidermal growth factor (EGF) by increased DNA synthesis. When hepatocytes were cultured in Leibovitz L-15 medium, hepatocyte response to EGF was low compared with those cultured in Williams' medium E or Koga's medium L. Furthermore, in L-15 medium, female rat hepatocytes showed almost no response to the mitogenic action of EGF compared with male rat hepatocytes. Addition of glutamic acid (1 to 20 mM) to EGF-containing L-15 medium not only enhanced DNA synthesis over 10-fold in both male and female hepatocytes, but eliminated the sex differences in DNA synthesis. Glutamic acid by itself did not stimulate DNA synthesis at any concentrations tested. In the presence of glutamic acid, EGF showed a dose-dependent (0.5 to 20 ng/ml) stimulation of DNA synthesis with maximal effect at 10 ng/ml. Almost the same effect was obtained with transforming growth factor alpha (0.5 to 20 ng/ml). Since glutamic acid did not affect 125I-EGF binding, the effect may occur internal to the receptor. These results suggest that glutamic acid modulates the sensitivity of the hepatocyte response to mitogens.

Original languageEnglish
Pages (from-to)243-252
Number of pages10
JournalBiomedical Research
Issue number4
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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