Ethanolamine modulates the rate of rat hepatocyte proliferation in vitro and in vivo

Abstract

A low molecular weight, heat-resistant hepatotrophic factor in an extract from the bovine intestinal mucosa was purified and identified as ethanolamine by structural analyses. The mode of action of ethanolamine in vitro and in vivo coincided with that of the crude extract of the tissue, indicating that ethanolamine is the active component. Ethanolamine synergistically elevated the stimulation of DNA synthesis in hepatocytes in primary culture when added together with a growth factor, such as epidermal growth factor, with the ED 50 being 20 M, although it showed little stimulatory effect by itself. Contrary to these in vitro results, the intraperitoneal administration of ethanolamine hydrochloride (24 mg of ethanolamine per kg of body weight) enhanced hepatocyte proliferation in regenerating rat livers after two-thirds hepatectomy without the administration of any growth factors. In the regenerating liver, hepatocyte proliferation may be initiated by an endogenous growth factor, but the supply of ethanolamine in circulation may not be sufficient for optimal hepatocyte proliferation; thus, the exogenous administration of ethanolamine may further enhance hepatocyte proliferation. Ethanolamine in circulation may be a humoral hepatotrophic factor.Previously we reported that the proliferation of hepatocytes in primary culture was synergistically stimulated by a low molecular weight (LMW, Ͻ1,000) and a high molecular weight (HMW, Ͼ10,000) factor that were derived from the bovine small intestine mucosa, separated by their solubility in methanol (1). The LMW factor synergistically enhanced the basal level of stimulation by the HMW factor, while it had little effect when added alone. Since the LMW factor could enhance the level of DNA synthesis in hepatocytes that were stimulated by epidermal growth factor (EGF) or hepatocyte growth factor (HGF), it acts by amplifying the effects of a growth factor. Contrary to the in vitro result, the LMW factor could stimulate hepatocyte proliferation in regenerating livers even when added alone. We speculate that an endogenous growth factor(s) is probably produced in the animals with the regenerating liver, but the supply of the LMW factor is below the optimal level, thus the exogenous supply of the LMW factor can further stimulate hepatocyte proliferation. The LMW factor may function as a humoral hepatotrophic factor for liver regeneration.We purified the LMW factor from the bovine small intestinal mucosa, and we identified it as ethanolamine (Etn). The commercially available Etn had effects identical to those of the LMW factor before purification; i.e., Etn synergistically stimulated the proliferation of hepatocytes in primary culture when added with the HMW factor, and it stimulated hepatocyte proliferation in the regenerating liver when administered alone. Etn can synergistically enhance DNA synthesis in hepatocytes when added with EGF, suggesting that it enhances the actions of hepatotrophic growth factors. Etn in circulation may function as a humoral hepatotrophic factor ...

Protective Effect of Ethanolamine on Hepatic Preneoplastic Alterations Induced by the Administration of <i>N</i>-Nitrosodiethylamine in Rats

“…Stimulation of cell proliferation by Etn is observed in the regenerating liver after partial hepatectomy, in which PE and PC synthesis is enhanced [8] [11]. In the regenerating liver, cell proliferation is stimulated by growth factors such as HGF and EGF [12] [13].…”

“…Etn enhances hepatocyte proliferation following hepatectomy [8]. Because Etn enhances PE synthesis in hepatocytes [11], it is speculated that Etn enhances The carcinogenic potency of NDA is attributed to its capabilities to induce DNA damage and oxidative stress.…”

“…Etn can act as a cofactor to enhance the activity of hepatocyte-specific growth factors [8]. Etn is a substrate for the synthesis of PE in many types of cells.…”

“…It was also reported that Etn enhances the proliferation of hepatocytes in primary culture by potentiating the action of growth factors [8] [9]. Although the mechanism of potentiation is unknown, one evident point is that PE and PC synthesis is apparently associated with cell growth activation by Etn in hepatocytes [10].…”

Effects of acute pre-treatment with ethanolamine on isoprenalineinduced myocardial infarction in adult Wistar rats

“…It has also been shown to increase hepatocyte proliferation in regenerating livers in vivo. (10) In the cardiovascular system, chronic Etn treatment in rats is associated with attenuation of hypercholesterolemia. (11) Furthermore, both chronic (12) and acute (13) pre-treatment with Etn protect the isolated rat heart from ischaemia-reperfusion injury.…”