Stimulation of Follistatin Production by Epidermal Growth Factor in Cultured Rat Hepatocytes

Production of follistatin in cultured rat hepatocytes was studied by measuring follistatin release with a protein-binding assay using [¹²⁵I]activin A. Follistatin was detected in conditioned medium of cultured hepatocytes. Ligand blotting using [¹²⁵I]activin revealed that follistatin released into the medium consisted of two different forms with molecular weight of approximately 40 K-Da. Epidermal growth factor (EGF) elicited dose-dependent increases in DNA synthesis and follistatin release. Dose-response relationship for EGF-induced follistatin release correlated well with that for EGF-induced DNA synthesis. In EGF-stimulated cells, a marked increase in DNA synthesis occurred after 48 hrs. Similarly, follistatin release was markedly augmented after 48 hrs. Amount of cell-bound follistatin was not changed by the treatment with EGF. These results indicate that cultured hepatocytes synthesize and release follistatin. The activin-follistatin system operates in cultured rat hepatocytes and may modulate DNA synthesis by altering the action of activin A.