Preferential suppression of insulin‐stimulated proliferation of cultured hepatocytes by somatostatin: Evidence for receptor‐mediated growth regulation

The role of somatostatin (SS‐14) in the regulation of rat liver regeneration was examined by using thymidine incorporation into hepatocyte DNA labeled with tritiated thymidine, a nuclear‐labeling index, and the binding of ¹²⁵I‐tyr¹¹‐SS‐14 to hepatocytes isolated at various times after partial hepatectomy. The data demonstrated no suppressive effect of SS‐14 on insulin and glucagon‐stimulated thymidine incorporation into hepatocyte DNA as early as 2 h after partial hepatectomy. These data were substantiated by a nuclear labeling index studies. At 2 h, ¹²⁵I‐tyr¹¹‐SS‐14 binding to its specific sites on isolated hepatocytes was undetectable. There was a time‐dependent increase in binding of ¹²⁵I‐tyr¹¹‐SS‐14 to hepatocytes obtained at various times after partial hepatectomy. There was a significant decrease in the number of binding sites after partial hepatectomy as determined by Scatchard analysis. The data were supported by autoradiography analysis of affinity labeled ¹²⁵I‐tyr¹¹‐SS‐14‐binding protein complex followed by SDS‐PAGE. SS‐14 also inhibited intracellular cAMP in hepatocytes obtained at 18 h after hepatectomy. The data are consistent with the hypothesis that SS‐14 participates via its own receptor in the regulation of the liver regeneration. © 1995 Wiley‐Liss, Inc.