Morphofunctional Differentiation in the Liver: 1. Influence of partial hepatectomy, cortisone and endotoxin on coordinated cellular activity during hepatic regeneration

Abstract

The influence of endotoxin and cortisone on the function of hepatic cells was studied in relation to the effect of partial hepatectomy on their activity. The overall rate of clearance of carbon (K) suffered a diminution within the first few hours after surgery but carbon uptake per unit weight tissue was elevated as a result of hepatic resection. The K values were increased by endotoxin (100°g i.p.) alone or together with cortisone (1 mg i.p.) but the hormone alone lowered the clearance rates in high doses (5 mg i.p.). Treatment with either substance increased liver weight over and above the control level in early phases of regeneration and lowered it in the later phases. The actions of cortisone and endotoxin were not additive on either process. As regards the influence of cellular cycle on hormonally modified gene activity, refractoriness to the hypertrophic effect of cortisone (5 mg i.p. a dose which lowered the K value at all times) developed soon after hepatic resection and continued for at least 36 h after surgery. These and other results indicate that the RE cells remain susceptible to external influences throughout the regenerative cycle and do not passively follow the behaviour pattern of parenchyma. An active contribution of RE cells is further supported by the observation that regeneration was accompanied by a progressive increase in spleen weight. Furthermore, because uptake and binding of cortisone to ‘specific’ receptors progressed at least as well as in control mice at all these time periods, the refractoriness to cortisone action must lie at some stage beyond uptake, processing or association of steroid with the appropriate receptor. These data indicate the necessity to consider the behaviour of individual cell types in order to comprehend the integrated responses observed during growth, development and differentiation in the liver.