EXPRESSION OF THYROTROPIN RECEPTOR AND THYROID-HORMONE RECEPTOR MESSENGER-RIBONUCLEIC-ACID IN NORMAL, HYPERPLASTIC, AND NEOPLASTIC HUMAN THYROID-TISSUE

In the first part of this study, we examined TSH receptor (TSHR) and thyroid hormone receptor (T(3)R beta) messenger ribonucleic acid (mRNA) levels in normal, hyperplastic, and neoplastic human thyroid tissue. Tumor specimens from patients with different thyroid carcinomas and thyroid adenomas, and tissues from patients with Graves' disease and from normal thyroid glands were analyzed by solution hybridization and Northern blot using complementary RNA probes. In the second part of the study, mRNA analysis of T(3)R was extended to include the expression levels of each of the four T(3)R isoforms alpha 1, alpha 2, beta 1, and beta 2. In neoplastic thyroid tissue such as papillary and follicular carcinomas, the expression of both TSHR and T(3)R beta mRNA per mu g total RNA was significantly lower than that in normal thyroid tissue. The decrease in T(3)R beta mRNA was shown to represent a specific and significant decrease in T(3)R beta 2 mRNA levels in particular, but also in the expression levels of T(3)R beta 1 mRNA. No differences were found in the expression levels of T3R alpha 1 or -alpha 2 mRNA. Furthermore, no differ ences in TSHR or T(3)R mRNA levels were found in thyroid tissue from patients with Graves' disease compared to normal thyroid tissue. It is concluded that the reduction of TSHR and T(3)R mRNA in specific neoplastic thyroid tissues might be associated with the differentiation state of these tumors and that the decrease in T(3)R mRNA levels is due to a specific decrease in the expression levels of the T(3)R beta gene.