RAPID APPEARANCE OF CONNEXIN 26-POSITIVE GAP-JUNCTIONS IN CENTRILOBULAR HEPATOCYTES WITHOUT INDUCTION OF MESSENGER-RNA AND PROTEIN-SYNTHESIS IN ISOLATED-PERFUSED LIVER OF FEMALE RAT

In the adult rat liver, the gap junction protein connexin 32 (Cx32) is evenly distributed in hepatocytes within the liver lobules, while con nexin 26 (Cx26) is: preferentially localized in hepatocytes in peripor tal zones. We report here that Cx26-positive gap junctions rapidly app ear in the centrilobular hepatocytes of adult female rat livers during a 30 minute perfusion of the liver through the hepatic portal vein wi th a 1:1 mixture of Dulbecco's modified Eagle's medium (DMEM) and oxyg en transport FC-43 fluid at a physiological flow rate without any chan ges in the distribution of Cx32. The change in the localization of Cx2 6 was closely related to that of E-cadherin, and there was no signific ant increase in the amounts of Cx26 protein and mRNA. The appearance o f Cx26 in the centrilobular hepatocytes was inhibited by treatment wit h cytoskeleton disrupters such as colchicine and cytochalasin B, and i ntracytoplasmic transport inhibitors such as brefeldin A. The liver pe rfusion induced the appearance of Cx26 in the centrilobular hepatocyte s only in female rats. Estrogen treatment of ovariectomized rats cause d the appearance of both Cx26 and E-cadherin in centrilobular hepatocy tes not only in the perfused liver but also in the non-perfused liver. Our results indicate that in the rat liver: (a) the localization of C x26 can be modulated by a post-translational mechanism; (b) E-cadherin may play an important role in the formation of gap junctions composed of Cx26; and (c) the formation of gap junctions is regulated by femal e steroid hormones.