Expression and function of thyroid hormone receptor variants in normal and chronically diseased human liver.

Abstract

As the liver represents a major target organ for thyroid hormone action, we compared the expression of thyroid hormone receptor (TR) alpha and beta variants in normal human liver and liver affected by primary biliary cirrhosis, sclerosing cholangitis, cryptogenic cirrhosis, and alcoholic cirrhosis (n = 6 in each group). Western blot analysis using specific polyclonal antibodies to alpha 1 or beta 1 TRs or to the related non-T3-binding c-erbA alpha 2 variant revealed abundant expression of TRs in normal and diseased liver, with no difference in size or abundance of TR proteins. Immunocytochemistry likewise revealed abundant nuclear expression of TR proteins in normal and diseased liver, with similar patterns and intensity of staining. Despite abundant TR protein expression, Northern blot hybridization of polyadenylated ribonucleic acid (RNA; 10 micrograms) to TR complementary DNAs revealed only a weak signal for c-erbA alpha 2 messenger RNA (mRNA). Comparison of the level of expression of the thyroid hormone-regulated mRNAs encoding T4-binding globulin, sex hormone-binding globulin, cortisol-binding globulin, and transthyretin in normal and diseased tissue revealed no significant difference, suggesting that hepatocellular expression of these mRNAs is maintained in chronic liver disease despite a marked reduction in circulating T3 concentrations.