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Published on: April 17, 2013
Desensitization in normal and neoplastic human thyroid cell lines
S S al-Sobhi1, E Y Soh, M G Wong
1Department of Endocrine Surgery, University of California San Francisco/Mount Zion Medical Center 94143-1674, USA.
Abstract:
Because some papillary thyroid cancers continue to grow when thyroid-stimulating hormone (TSH) levels are suppressed, we questioned whether desensitization (i.e., a decreased cAMP response to repeat stimulation with TSH) occurs in normal and neoplastic thyroid tissue. If desensitization does occur, is it similar or different in these human thyroid cells? Normal and papillary thyroid cancer cells from the same patient 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 there was an 11-fold mean increase in cAMP production at 4 hours, and all thyroid cultures responded. In neoplastic cells cAMP production increased 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 desensitization 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 the five neoplastic thyroid cell cultures. Thus when normal thyroid and neoplastic cells from the same patients were studied, greater desensitization occurred in the normal cells (75% vs. 17%). These studies document that there is greater desensitization in normal tissue than in neoplastic thyroid tissue, which may account for the increased growth of thyroid neoplasms in the presence of ever-changing low levels of TSH.
Insights
Normal thyroid cells show greater desensitization to thyroid-stimulating hormone (TSH) than papillary thyroid cancer cells. This difference in cAMP response may explain why thyroid tumors grow even with suppressed TSH levels.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Papillary thyroid cancers can progress despite suppressed thyroid-stimulating hormone (TSH) levels.
- The cellular response of normal and cancerous thyroid tissue to repeated TSH stimulation is not fully understood.
Purpose of the Study:
- To investigate whether desensitization to TSH occurs in normal and neoplastic human thyroid tissue.
- To compare the extent of TSH desensitization between normal thyroid cells and papillary thyroid cancer cells from the same patients.
Main Methods:
- Cultured normal and papillary thyroid cancer cells from the same patients.
- Measured cyclic adenosine monophosphate (cAMP) production and cell growth in response to varying doses of TSH.
- Assessed the cAMP response to a second TSH stimulus to determine the degree of desensitization.
Main Results:
- Both normal and neoplastic thyroid cells responded to TSH with increased cAMP production and growth in a dose-dependent manner.
- Normal thyroid cells exhibited significant TSH desensitization (up to 75% decrease in cAMP response) in all cultures.
- Neoplastic thyroid cells showed minimal desensitization (up to 17% decrease in cAMP response), occurring in only two of five cultures.
Conclusions:
- Normal thyroid tissue demonstrates significantly greater TSH desensitization compared to neoplastic thyroid tissue.
- The reduced desensitization in thyroid cancer cells may contribute to their sustained growth under fluctuating TSH levels.
- These findings highlight a potential mechanism underlying thyroid tumor progression in the presence of suppressed TSH.
