Organ specific expression of thyroid hormone receptor mRNA and protein in different human tissues

The major physiologic effect of thyroid hormone is thought to be initiated by the binding of T3 to the DNA binding thyroid hormone receptor (TR). The aim of this study has been to characterize the organ specific expression of thyroid hormone receptor mRNA, as well as its protein distribution and mol ecular weight in man. Determination of TR alpha 1, alpha 2, beta 1 and beta 2 mRNA molecular size was performed using Northern blot analysis in the hu man heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancre as. TR alpha 1, alpha 2 and beta 1 protein expression was characterized by Western blot analysis of human tissues. TR alpha 1 mRNA of 4.9 kb was detec ted in all 8 tissues analyzed, with varying abundance in the various tissue s. TR alpha 2 mRNA was detected in 2 different sizes, with higher intensity at 5.7 and lower intensity at 3.2 kb. There were, however, multiple TR bet a 1 mRNA of 8, 2 and 1 kb detected. TR beta 1 transcripts of 2 kb and 1 kb showed an organ specific pattern of expression, Multiple TR beta 2 mRNA of 6.6, 5.2, 2.5 and 2.4 kb were detected, as well as a unique 1 kb transcript , in the heart. TR beta 2 transcripts also displayed tissue specific expres sion. Western blot analysis displayed a single band of 48 kD for TR alpha 1 . The abundance of the TR alpha 1 immunoreactive band was highest in the he art, brain, kidney and skeletal muscle, and lowest in the liver, placenta a nd lung, while no signals were detected in the spleen. The TR alpha 2 speci fic antibody detected a band of 58 kD in all the tissues analyzed. The rela tive intensity of the immunoreactive TR alpha 2 band detected was highest i n the placenta and lung, with a medium concentration range in skeletal musc le, the heart and kidney The TR alpha 2 protein concentration was lowest in the spleen, liver and brain. Human TR beta 1 protein was detected as 55 an d 52 kD bands, as well as a unique band of 45 kD in heart. The 52 kD band w as detected in all tissues except the kidney and spleen. The 55 kD band was not detected in the brain or liver. Both the 55 and 52 kD TR beta 1 immuno reactive bands were detected in the placenta, Lung, heart and skeletal musc le with similar intensity. In conclusion, specific patterns of TR mRNA and protein expression revealed characteristic organ distributions of each subtype. Unique cardiac express ion was observed for TR beta(2) mRNA and for TR beta(1) protein.