ENHANCEMENT OF LIVER-CELL GAP JUNCTION PROTEIN EXPRESSION BY GLUCOCORTICOIDS

Gap junctional intercellular communication (GJIC) and the expression o f gap junction proteins (connexins) may be involved in growth regulati on and neoplastic transformation. The mechanisms of connexin gene regu lation in normal and neoplastic tissues are poorly understood. In this study, the glucocorticoids, dexamethasone and hgdrocortisone, enhance d fluorescent dye-coupling in primary cultured rat hepatocytes and MH( 1)C(1) rat hepatoma cells. Other types of steroids (beta-estradiol, te stosterone, aldosterone and progesterone) had no effect. Northern blot , Western blot, nuclear run-on and immunohistochemical analyses showed that glucocorticoids enhanced the expression of connexin32 in these c ells in a dose- and time-dependent fashion. Connexin26 expression was also enhanced slightly by dexamethasone in hepatocytes, but not MH(1)C (1) cells. Connexin43 expression in these cells was not affected by st eroids. In WB-F344 rat liver epithelial cells, which were highly coupl ed and expressed high levels of connexin43 and no detectable connexin3 2 or connexin26, dexamethasone had no effect on coupling or connexin e xpression. These results indicate that dye-coupling and the expression of connexin32 and connexin26, but not connexin43, were upregulated by glucocorticoids in a cell-specific manner. These effects on GJIC and connexin expression may be involved in the induction of hepatic differ entiation and inhibition of growth.