STIMULATION OF FOLLISTATIN PRODUCTION BY EPIDERMAL GROWTH-FACTOR IN CULTURED RAT HEPATOCYTES

Production of follistatin in cultured rat hepatocytes was studied by m easuring follistatin release with a protein-binding assay using [I-125 ]activin A. Follistatin was detected in conditioned medium of cultured hepatocytes. Ligand blotting using [I-125]activin revealed that folli statin released into the medium consisted of two different forms with molecular weight of approximately 40 K-Da. Epidermal growth factor (EG F) elicited dose-dependent increases in DNA synthesis and follistatin release. Dose-response relationship for EGF-induced follistatin releas e correlated well with that for EGF-induced DNA synthesis. In EGF-stim ulated 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 cultur ed rat hepatocytes and may modulate DNA synthesis by altering the acti on of activin A. (C) 1994 Academic Press, Inc.