Insulin and catecholamines act at different stages of rat liver regeneration.

Insulin and catecholamines are known to exert effects on hepatocyte growth and metabolism. The binding of insulin, the plasma levels of insulin (INS), and the plasma catecholamine levels of epinephrine (EPI) and norepinephrine (NE) were measured during liver regeneration after partial hepatectomy (PH). A significant decrease (p < 0.05) of INS receptor binding capacity was found at 1, 2, and 3 days after operation. A single insulin injection (2.5 IU/kg body weight) at 24 h after sham operation or partial hepatectomy did not affect these changes of INS binding to hepatocytes. The plasma insulin and glucose levels were similar in both hepatectomized and sham-operated rats. Within 20 min after liver resection or sham operation, plasma NE and EPI concentrations increased rapidly. Then, a significant decrease was observed in plasma catecholamine levels at 1 h after laparotomy and PH. In both groups, laparotomized and partially hepatectomized plasma levels of NE at 4 h reached control values and remained unchanged at the 4- and 24-h periods. After PH, the levels of EPI remained elevated at 4 h in comparison with laparotomy. Adrenal tyrosine hydroxylase mRNA levels were significantly elevated at 4 h in both PH and sham-operated groups. These results suggest that signals that are initiated by catecholamines and transduced through second messengers presumably participate in the trigger mechanism of liver regeneration, while insulin (considered as a secondary mitogen) enhances a stimulus for liver regeneration.

Effect of 3,5,3'-L-triiodothyronine on hepatic ornithine decarboxylase and thymidine kinase activity in rat after partial hepatectomy.

Partial hepatectomy (60%) led to the biphasic increase (first one at 4 h and second one at 48 h) of ornithine decarboxylase activity in the remnant rat liver. Daily administration of 3,5,3'-L-triiodothyronine (T3) (10 micrograms/100 g) to rats for 7 days before partial hepatectomy had little effect on the enzyme activity. At five days, ornithine decarboxylase activity declined to control level (sham operated controls) and its activity was significantly enhanced by T3. Ornithine decarboxylase gene expression in the rat liver (examined by Northern blot analysis using poly A+ mRNA) started to increase 4 h after partial hepatectomy, remained elevated for 48 h and decreased after 5 days. Its activity was not altered by T3 treatment. The activity of thymidine kinase increased progressively after partial hepatectomy, but its peak value was delayed by T3 administration. Plasma prolactin levels increased within 5-15 min after liver resection, then declined to control values and increased 24 h after the surgery. The data demonstrate that the changes in ornithine decarboxylase activity in the rat liver after partial hepatectomy might result from the direct effect of prolactin on the activity of enzyme rather than from its induction by hormone. Triiodothyronine administration altered both ornithine decarboxylase and thymidine kinase activities suggesting that T3 appears to regulate ornithine decarboxylase activity at post-translational level.

Changes in plasma catecholamine and corticosterone levels and gene expression of key enzymes of catecholamine biosynthesis in partially hepatectomized rats.

OBJECTIVE: To reexamine the possible role of catecholamines and corticosterone in the early period of liver regeneration after partial hepatectomy (PH)in conscious cannulated rats under carefully controlled conditions which would allow to obtain reliable information about sympathetic-adrenomedullary function after PH in the rat in vivo. METHODS: Plasma levels catecholamines (epinephrine - EPI, norepinephrine - NE) were estimated by radioenzymatic assay and these of corticosterone by competitive protein binding assay. The total RNA was isolated from the adrenals and tyrosine hydroxylase (TH) mRNA expression was estimated by hybridisation with cDNA after Northern blot. The level of immunoreactive protein was measured by using a monoclonal antibody to rat TH, visualized by Western light chemiluminescent detection system and analyzed by densitometry. The level of TH in adrenals was estimated with the aid of 3H-tyrosine and TH cofactor DL-6-methyl-5,6,7,8-tetrahydropterine and the formed radioactive water was measured by scintillation spectometry. RESULTS: The plasma level of norepinephrine (NE), epinephrine (EPI) and corticosterone rapidly increased 20 min. after PH or sham operation (laparotomy). Although the increase of plasma NE was about the same after both PH and laparotomy, that of EPI and corticosterone in PH rats was significantly higher as compared to the laparotomy. One hour after the surgery plasma NE levels in both groups decreased to the basal value and remained still unchanged 4 and 24 h later. At the interval of 4h the plasma level of EPI was higher than in laparotomized controls, but after 24 h the EPI levels returned to basal values. Adrenal tyrosine hydroxylase (TH) mRNA level was significantly elevated in both PH and laparotomized rats, however 24 h after the surgery they returned to the baseline. Adrenal TH immunoprotein levels and TH activity were significantly elevated in both groups 4 h after the surgery, while 24 h later they returned to the baseline in laparotomized rats bur remained elevated in PH rats. Adrenal phenylethanolamine N-methyl-transferase (PNMT) mRNA levels were increased 4 h after both the PH and laparotomy and declined within 24 h. CONCLUSIONS: The first peak of catecholamine and corticosterone levels might result from unspecific stressor associated with the surgery. These levels could be accompanied with the mechanism of the rat liver regeneration. Prolonged elevations of EPI found after PH seems to be specific for liver regeneration indicating that the rise in the adrenal TH mRNA appears to be translated into immunoreactive protein which further leads to the elevation of TH activity. These results contrast markedly with previous studies indicating that the regeneration is modulated predominantly by norepinephrine.