Regulation of hepatocyte gap junctions by steroids and tumor promoters

The present studies were conducted to determine the mechanisms by which glucocorticoid and coculture with liver epithelial cells enhanced primary cultured hepatocyte GJIC and how barbiturate liver tumor promoters decreased it.; The glucocorticoids, dexamethasone and hydrocortisone, increased GJIC in primary cultured rat hepatocytes in a dose- and time-dependent fashion in pure and/or cocultured hepatocyte systems. The mechanisms of these effects involved the enhancement of CX32 and CX26 gene expression by the hepatocytes. Long-term connexin expression and GJIC by hepatocytes was enhanced by coculture with WB-F344 rat liver epithelial cells. This enhancement required heterotypic cell-cell contact in the cocultures. An enhancement of hepatocyte GJIC was not seen when hepatocyte and WB cells were physically separated.; The down regulation of GJIC by barbiturate liver tumor promoters occurred in dose- and time-dependent fashions. Strong liver tumor promoting barbiturates, phenobarbital and sodium barbital, and a weak promoter, amobarbital, decreased hepatocyte GJIC after long-term treatment (14d). The nonpromoter, barbituric acid, had no effect on hepatocyte GJIC. Cocultured WB cell were not affected in this way. The barbiturates did not affect hepatocyte or WB cell connexin expression. These results indicate that barbiturates reduce GJIC in a cell-specific manner without affecting connexin expression.