α₁-ACID GLYCOPROTEIN AND α₁-ANTITRYPSIN AS MITOTIC INHIBITORS IN REGENERATING RAT LIVER

Abstract

Time course changes in the concentration of the plasma proteins, especially α₁-acid glycoprotein and α₁-antitrypsin, after partial hepatectomy were investigated. The concentration of α₁-acid glycoprotein rose steadily to the highest value, about four-fold of that of normal non-hepatectomized rats, at 27.5hr after partial hepatectomy, indicating excretion of the protein from hepatocytes in the residual liver during a very early period after partial hepatectomy, before hepatocytic mitosis, and thereafter fell slowly. The concentration of α₁-antitrypsin decreased sharply to one-sixth of that of the non-operated control rats, at 18hr after partial hepatectomy, 10hr before the peak of mitosis, and thereafter rose steadily to the highest value above the control at 168hr, when the mitosis almost ended, suggesting a close correlation of the protein to the occurrence and suppression of mitosis of the hepatocyte.
These results suggest the existence of a double-layered pattern of humoral factors involved in cell division; α₁-acid glycoprotein may be a primary mitotic inhibitor, whose intracellular concentration over a critical level inhibits cell division and, in contrast, α₁-antitrypsin may be one of secondary mitotic inhibitors, whose extracellular concentration below a critical level facilitates the excretion of the primary mitotic inhibitor from the cell in question, allowing cell division, and that over a critical level impedes the excretion of the primary one from the cell in question, inhibiting cell division.
Based on these findings, the essential part of the regulatory mechanism of cell division in the regenerating rat liver is concretely discussed.