Hepatocyte conditioned medium modulates the response of primary rat hepatocyte cultures to epidermal growth factor

Primary hepatocytes may produce autocrine growth trigger(s) with or without a mitogenic stimulus. We explored the potential of hepatocyte conditioned medium--from untreated quiescent cultures--to modulate the DNA synthetic responses induced by EGF. The EGF-induced responses were similar when EGF was continuously or transiently (3 h) present. Conditioned medium (CM) from 48 h hepatocyte culture was the most effective in eliciting thymidine incorporation into hepatocyte DNA. At the same time the conditioned medium from hepatocyte cultures stimulated lymphocyte DNA synthesis at levels much lower than those observed using PHA, a specific lymphocyte inducer. The maximal EGF-binding by intact hepatocytes was also significantly increased in the presence of conditioned medium (48 h). We therefore suggest that hepatocytes produce autocrine growth trigger(s) which might be in part responsible for the regulation of the in vitro and/or in vivo hepatocyte proliferation.