Elevated hepatic glucocorticoid receptor expression during liver regeneration in rats.

In rats within the first week of partial hepatectomy reconstruction of the normal histological structure of the liver already starts. To approach the possible role of endogenous glucocorticoids in the process of regeneration we measured the changes in the expression of steroid glucocorticoid receptor gene after various regeneration intervals. After partial hepatectomy, between 0.5 168 hours from the surgery, the gene expression (mRNA) of glucocorticoid receptor was determined by reverse transcription followed by PCR and normalized to that of glycerolphoshate dehydrogenase. Two peaks of glucocorticoid receptor mRNA were detected first, between 3 and 6 hours (first peak) and a second between 24 and 36 hours. Immunoreactive glucocorticoid receptor was detected by immunohistochemistry using monoclonal anti-glucocorticoid receptor. Three days after the surgery immunohistochemical studies showed substantially more immunoreactive GcR protein in the regenerated liver than in the controls. These semiquantitative data provide evidence suggesting elevation of glucocorticoid receptor expression during regeneration of liver at mRNA and protein levels.

Is cancer promotion associated with dysfunction in co-operation between differentiated cells?

In a selection-based computer model system we demonstrated that deteriorating cellular co-operation between differentiated cells could result in positive selection for initiated cells of high proliferative capacity. The ratio of the initiated cells to their normal counterparts increased from 0.47 to 0.63 when the strength of co-operation decreased to one hundredth. The correlation proved to be significant. A number of bioactive substances involved in cell-to-cell communication are already registered as cocarcinogens. Whether this approach can explain the role of other promoting agents remains to be answered. It is also possible that the high incidence rate of old-age cancer may be in part accounted for by this kind of co-operational failure during senescence.