l-Ornithine decarboxylase (l-ornithine carboxy-lyase, EC 22.214.171.124) activity was studied in the isolated perfused rat liver. Activity was lost rapidly on perfusion in the presence of cycloheximide to block protein synthesis but the decline was retarded in the presence of high levels of amino acids. An even more rapid loss of activity was produced by the addition of 5 mM putrescine to the perfusion medium. In this case, activity was lost with a half-time of 15 min. Perfusion for 3 h in a recirculating system in the presence of 10 times normal plasma levels of amino acids led to a 4-5-fold increase in ornithine decarboxylase activity during the final hour of perfusion. This effect was also seen in perfusion of livers from hypophysectomized or adrenalectomized rats. Growth hormone produced an additional increase of activity during a 3 h perfusion. Although amino acids were required for the increased activity, a similar increase could not be produced by addition of l-ornithine or dihydro-l-orotate to the perfusion medium. Since putrescine levels fell during the first 2 h of perfusion it is suggested that the increase of ornithine decarboxylase activity was in response to the lowered putrescine levels. Addition of putrescine to the perfusion medium at any time produced a rapid revesal of the increase in activity. After perfusion in the presence of putrescine a non-diffusible inhibitor of ornithine decarboxylase was found in liver extracts. These data indicate the value of the isolated perfused liver in studies of the control of onithine decarboxylase and strongly support the hypothesis that putrescine levels may play a key role in regulating ornithine decarboxylase activity and polyamine synthesis.
All Science Journal Classification (ASJC) codes