Background/aims: The proliferation rate of adult rat liver is normally very low. It is markedly enhanced during compensatory regeneration, e.g. after partial hepatectomy, or after administration of certain growth promoters, e.g. cyproterone acetate. These two types of liver cell proliferation appear to differ, since the expression of immediate early genes is induced during compensatory regeneration but not after cyproterone acetate treatment. The transcription factor C/EBP alpha, which has been associated with hepatocyte differentiation and growth arrest, is suppressed during compensatory regeneration. In contrast, C/EBP beta, associated with acute phase reaction, is increased during regeneration. We have investigated the effects of the liver growth promoter cyproterone acetate on the hepatic expression of C/EBP alpha and C/EBP beta.
Methods: Adult male rats received either cyproterone acetate treatment or were subjected to partial hepatectomy. Livers were obtained at different time intervals for measurement of C/EBP alpha and C/EBP beta mRNA with solution hybridization/RNAse protection assay, and C/EBP alpha and C/EBP beta content with immunoblotting.
Results: The levels of both C/EBP alpha and C/EBP beta mRNA and the corresponding immunoreactivities were unchanged 2-48 h after injection of cyproterone acetate. The levels of C/EBP alpha mRNA and immunoreactivity were significantly suppressed 10-18 h and 18-26 h after partial hepatectomy, respectively. The levels of C/EBP beta mRNA and immunoreactivity were enhanced during compensatory regeneration 2 h after partial hepatectomy.
Conclusions: Liver cell proliferation during regeneration, but not in response to cyproterone acetate treatment, is associated with changes in C/EBP alpha and C/EBP beta expression. This further supports the notion that changes in expression of transcription factors during liver growth in vivo are dependent on the growth inducer.