EXPRESSION AND FUNCTION OF THYROID-HORMONE RECEPTOR VARIANTS IN NORMAL AND CHRONICALLY DISEASED HUMAN LIVER

As the liver represents a major target organ for thyroid hormone actio n, we compared the expression of thyroid hormone receptor (TR) alpha a nd beta variants in normal human liver and liver affected by primary b iliary cirrhosis, sclerosing cholangitis, cryptogenic cirrhosis, and a lcoholic cirrhosis (n = 6 in each group). Western blot analysis using specific polyclonal antibodies to alpha 1 or beta 1 TRs or to the rela ted non T-3-binding c-erbA alpha 2 valiant revealed abundant expressio n of TRs in normal and diseased liver, with no difference in size or a bundance of TR proteins. Immunocytochemistry likewise revealed abundan t nuclear expression of TR proteins in normal and diseased liver, with similar patter ns and intensity of staining. Despite abundant TR prot ein expression, Northern blot hybridization of polyadenylated ribonucl eic acid (RNA; 10 mu g) to TR complementary DNAs revealed only a weak signal for c-erbA alpha 2 messenger RNA (mRNA), Comparison of the leve l of expression of the thyroid hormone-regulated mRNAs encoding T-4-bi nding globulin, sex hormone-binding globulin, cortisol-binding globuli n, and transthyretin in normal and diseased tissue revealed no signifi cant difference, suggesting that hepatocellular expression of these mR NAs is maintained in chronic liver disease despite a marked reduction in circulating T-3 concentrations.