PMID- 8097889 OWN - NLM STAT- MEDLINE DCOM- 19930603 LR - 20190830 IS - 0167-0115 (Print) IS - 0167-0115 (Linking) VI - 44 IP - 1 DP - 1993 Mar 5 TI - The effects of transforming growth factor alpha and somatostatin on regenerating hepatocytes in the rat. PG - 49-59 AB - Transforming growth factor alpha (TGF alpha) stimulates DNA synthesis in adult rat hepatocytes, and plays a physiological role after partial hepatectomy by an autocrine mechanism. Somatostatin (SS-14) is a potent inhibitor of gastrointestinal function and inhibits proliferation in various cell types. We examined the proliferative effect of TGF alpha and the inhibitory effect of SS-14 on hepatocytes isolated at various times after partial hepatectomy. To study the mechanism of SS-14 further, we treated rats with the long acting SS-14 analog, octreotide, before or after 70% hepatectomy to determine whether or not a differential effect could be seen. We confirmed the proliferative effects of TGF alpha, and the inhibitory action of SS-14 in the early phase of liver regeneration in vitro. Regenerating hepatocytes isolated from hepatectomized livers respond to TGF alpha only at early time points (2 h) but do not respond to SS-14. In addition, the long acting SS-14 analog, octreotide, inhibited hepatic regeneration only when administered prior to hepatectomy. We conclude that exogenous peptide stimulation is effective only in the early phase of the hepatic proliferative response. After the initial changes brought about by hepatectomy, subsequent steps of the regenerative process appear refractory to external stimuli. FAU - Hashimoto, M AU - Hashimoto M AD - Department of Surgery, University of Michigan Medical School, Ann Arbor. FAU - Kothary, P C AU - Kothary PC FAU - Raper, S E AU - Raper SE LA - eng PT - Journal Article PL - Netherlands TA - Regul Pept JT - Regulatory peptides JID - 8100479 RN - 0 (Growth Inhibitors) RN - 0 (Transforming Growth Factor alpha) RN - 51110-01-1 (Somatostatin) RN - 9007-49-2 (DNA) RN - RWM8CCW8GP (Octreotide) SB - IM MH - Animals MH - Cells, Cultured MH - DNA/biosynthesis/drug effects MH - Growth Inhibitors/pharmacology MH - Hepatectomy MH - Liver/cytology/drug effects/metabolism MH - Liver Regeneration/*drug effects MH - Male MH - Octreotide/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Somatostatin/*pharmacology MH - Transforming Growth Factor alpha/*pharmacology EDAT- 1993/03/05 00:00 MHDA- 1993/03/05 00:01 CRDT- 1993/03/05 00:00 PHST- 1993/03/05 00:00 [pubmed] PHST- 1993/03/05 00:01 [medline] PHST- 1993/03/05 00:00 [entrez] AID - 0167-0115(93)90129-V [pii] AID - 10.1016/0167-0115(93)90129-v [doi] PST - ppublish SO - Regul Pept. 1993 Mar 5;44(1):49-59. doi: 10.1016/0167-0115(93)90129-v.