Hepatopoietins A and B and hepatocyte growth.

Serum from control or partially hepatectomized rats contains only two substances associated with stimulation of DNA synthesis in primary cultures of hepatocytes in serum free conditions. Hepatopoietin A is a large (105,000 kDa in monomeric form) heparin binding growth factor that is a heterodimer of two polypeptide chains (70,000 and 35,000 kDa). Another heparin binding growth factor, acidic FGF, also stimulates hepatocyte DNA synthesis but at a level comparable to half that of HPTA. These findings, along with recent observations of stimulation of liver growth and hepatoma formation in mice transgenic for the tat gene of the AIDS virus and overproducers of the heparin binding factor hst/KS3, raise the issue of the overall importance of different heparin binding growth factors in the control of hepatic growth regulation. Hepatopoietin B is a glycolipid that also acts as a complete hepatocytic mitogen. The role of the above substances as well as the role of norepinephrine, acting as a mitogenic trigger for stimulation of the rapid early phenomena associated with liver regeneration, is discussed.