Human Recombinant Thyrotropin Fails to Induce Thyroid Cell Proliferation
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Background
Iatrogenic subclinical thyrotoxicosis that leads to thyrotropin (TSH) suppression is required in the management of patients with papillary thyroid carcinoma (PTC) due to the mitogenic effects of TSH. Nevertheless, the available evidence supporting this practice is limited and weak. Our study seeks to explore the impact of human recombinant thyrotropin (rh-TSH) at clinically relevant doses on cell cultures of human normal and PTC follicular cells.
Materials and Methods
A human normal thyroid cell line (Nthy-Ori 3-1) and cancerous cell lines (K1 and TPC-1) were transformed using the Lenti-X Tet-on Advanced system to overexpress the thyrotropin receptor (TSHR). Transformed and non-transformed cells were treated with escalating doses of rh-TSH (5–1,000 μIU/mL) under various conditions, such as the presence or absence of 0.5 U/mL insulin. Cell proliferation was estimated by the crystal violet assay, migration of the cells was assessed by a scratch test, and the expression levels of TSHR and thyroglobulin (Tg) were determined using RT-PCR and Western Blot.
Results
Under the in-vitro culture conditions employed, rh-TSH was not adequate to induce either the proliferation rate or the migration potential in transformed and non-transformed cells. On the contrary, Tg expression was increased with rh-TSH under the same culture conditions.
Conclusion
Our experiments indicate that clinically relevant concentrations of rh-TSH cannot induce proliferation and migration in both normal and cancerous cell lines, even after overexpression of TSHR. Further research is warranted to dissect the molecular mechanisms underlying these effects. These results could translate into better management of PTC patients.
