DESENSITIZATION IN NORMAL AND NEOPLASTIC HUMAN THYROID-CELL LINES

Because some papillary thyroid cancers continue to grow when thyroid-s timulating hormone (TSH) levels are suppressed, we questioned whether desensitization (i.e., a decreased ck;MP response to repeat stimulatio n with TSH) occurs in normal and neoplastic thyroid tissue. If desensi tization does occur, is it similar or different in these human thyroid cells? Normal and papillary thyroid cancer cells from the same patien t were cultured as we have previously described Normal and neoplastic thyroid tissues responded to TSH (0.01-10.0 mU/ml) by increasing cAMP production and growth in a dose-dependent manner. In normal cells ther e was an 11-fold mean increase in cAMP production at 4 hours, and all thyroid cultures responded. In neoplastic cells cAMP production increa sed from 1.5-fold to 3.0-fold with a mean 2.0-fold increase at 4 hours . In normal thyroid cells the cAMP response to a second TSH stimulus ( desensitization) decreased up to 75% (range 25-75%), and desensitizati on occurred in all normal thyroid cell cultures. In neoplastic thyroid cells, however, the cAMP response to a second TSH stimulus decreased up to 17% (range 0-17%); and desensitization occurred in only two of t he five neoplastic thyroid cell cultures. Thus when normal thyroid and neoplastic tells from the same patients were studied, greater desensi tization occurred in the normal cells (75% vs. 17%). These studies doc ument that there is greater desensitization in normal tissue than in n eoplastic thyroid tissue, which may account for the increased growth o f thyroid neoplasms in the presence of ever-changing low levels of TSH .