Evidence for epithelial-mesenchymal interactions mediating glucocorticoid effects in developing chick liver....

When trypsin-dissociated liver cells from 17-day chick embryos were grown in regular minimum essential medium, mixed hepatocyte-fibroblast cultures resulted. When D-valine was substituted for L-valine in this medium, fibroblast growth was suppressed, leaving virtually pure hepatocyte cultures. Tyrosine aminotransferase activity is induced by cortisol in mixed cultures. No induction of enzyme activity is observed with cortisol exposure to hepatocytes, grown in D-valine. However, when cortisol-containing medium is conditioned by pre-incubation with mixed cells and then transferred to hepatocytes, tyrosine aminotransferase activity is induced. Enzyme activity is also induced in mixed cells incubated in D-valine medium in the presence of cortisol. It appears that a substance produced in the presence of fibroblasts exposed to cortisol is capable of inducing tyrosine aminotransferase activity in hepatocytes. This activity, which we have termed fibroblast hepatocyte factor, is heat stable, of low molecular weight, and antigenically different from fibroblast pneumonocyte factor, a factor similar to that produced by lung fibroblasts exposed to cortisol.