Zonal expression of the thyroid hormone receptor α isoforms in rodent liver

Abstract

Many metabolic processes occur simultaneously in the liver in different locations along the porto-central axis of the liver units. These processes are often regulated by hormones, one of which is thyroid hormone which for its action depends on the presence of the different isoforms of the thyroid hormone receptor (TR). These are encoded by two genes: c-erbA-α encoding TRα1 and TRα2 and their respective Δ isoforms, and c-erbA-β which encodes TRβ1, TRβ2 and TRβ3. We recently found a zonal (pericentral) expression of and a diurnal variation in the TRβ1 isoform in rat liver. We were therefore also interested to see whether TRα1 and TRα2 expression showed similar characteristics. For this reason we raised both polyclonal and monoclonal antibodies against TRα1 and TRα2 isoforms and characterised these. Antibody specificity was tested using Western blots and immunohistochemistry in liver of TR isoform-specific knockout animals. Using these antibodies we found that the TRα1 and TRα2 isoforms are zonally expressed around the central vein in rat liver. The experiments, show that the portal to central gradient of TRα1 is broader than that of TRβ1. Moreover, the expression of the TRα2 protein showed a diurnal variation with a peak in the afternoon when the animals are least active whereas no such variation was found for the TRα1 protein. From our data it appears that both the TRα1 and TRα2 isoforms show a zonal distribution in liver. This finding, together with the observed diurnal rhythm, has major implications for interpreting and timing experiments concerning the TR and its downstream actions in liver.