The nonportal origin of the factors initiating hepatic regeneration.

To determine the site of origin of the factors that initiate deoxyribonucleic acid (DNA) synthesis in the liver after partial hepatectomy, normal rats were cross-circulated with totally hepatectomized rats. Half of the hepatectomized rats had also undergone excision of all of the portal organs. After 48 hours of cross-circulation, active DNA synthesis and other evidences of hepatic regeneration were found in normal rats cross-circulated with the hepatectomized portally eviscerated rats. This demonstrates that a blood-borne factor that does not arise from the portal organs is capable of initiating hepatic regeneration. When a normal rat was cross-circulated with a hepatectomized rat with the portal organs still present, hepatic regeneration occurred but was significantly less than when the portal organs had been removed. It is postulated that under these experimental conditions portal factors from the normal rat have a permissive role that allows active regeneration when initiating factors are furnished from the hepatectomized rat. Additional portal organs in the hepatectomized rat decreased DNA synthesis, possibly by alterations of the insulin/glucagon ratio.