Circadian synchronization of liver regeneration in adult rats: the role played by adrenal hormones

Abstract

The role played by the adrenal hormones in the regulation of liver proliferation in adult rats was investigated under various experimental conditions.In untreated control groups, cell growth was very low and endogenous corticosterone levels showed a clearly-defined circadian rhythm with a peak in the evening. Adrenalectomy depressed the level of endogenous corticosterone immediately and the growth rate of the liver increased significantly. We were able to prevent this effect by repeated injections of corticosterone at physiological doses.After a 1/3 hepatectomy and a sham-operation, the corticosterone blood level maintained its normal circadian pattern with the exception of a transient increase during the first two post-operative hours. After a hepatectomy of this kind, a negative correlation was found to exist between the adrenal hormone level and the waves of DNA synthesis; the subsequent mitoses appeared in two successive circadian waves of decreasing amplitude, a maximum value being reached in the morning. In rats submitted to a 1/3 hepatectomy and an adrenalectomy simultaneously, the endogenous corticosterone level fell significantly after a post-operative peak. The regenerating pattern was completely different from that induced by 1/3 hepatectomy alone. The rise in the labelling index began earlier and rose to significantly higher values; it was then followed by a single large mitotic wave without any circadian rhythm.These results favour the hypothesis that adrenal hormones have a significant effect on the negative control of liver regeneration. Circadian changes in the corticosterone level were responsible for the nycthemeral pattern observed in the regenerating liver after a partial hepatectomy. The results show a marked inhibition of the G,-S transition, particularly in the evening, when the endogenous corticosterone concentration was at its highest. Also discussed is the relationship between corticoids and 'chalones', which synergetically inhibit the passage from Go into the cell cycle.We have previously shown that the circadian synchronization of hepatic cell proliferation and specific enzyme activities are triggered from the 20th day of life onwards (Barbason, Van Cantfort & Houbrechts, 1974). This corresponds to the maturation and the circadian activity of

Molecular and cellular features of hepatic regeneration

“…The importance of portal venous blood flow to basal hepatocyte proliferation is clear, however, as evidenced by the hepatic atrophy that occurs when portal blood flow is absent [6,7]. Additionally, circadian peaks of DNA synthesis occur postprandially, during times of peak portal venous blood flow [8,9].…”

The quest for liver progenitor cells: A practical point of view

“…A circadian rhythm of liver regeneration exists [14,82] e.g. the induction of liver regeneration by various hepatotoxins should preferentially be initiated at a standardized time of day (between 9:00 and 12:00 in the morning).…”

A partial hepatectomy results in altered expression of clock-related and cyclic glyceraldehyde 3-phosphate dehydrogenase (GAPDH) genes

“…Barbason et al (Barbason et al, 1989) have previously demonstrated that, following partial hepatectomy, the number of mitotic cells in the liver showed daily fluctuations from high levels during the early day to lower levels at night. During mitosis, transcription is almost completely suppressed, which may contribute to the overall decrease in gene expression.…”