Bruno R et al. (2005) Modulation of thyroid-specific gene expression in normal and nodular human thyroid tissues from adults: an in vivo effect of thyrotropin. J Clin Endocrinol Metab [10.1210/jc.2005-0800]

Complex mechanisms regulate thyroid physiology. Although some information is available, the data from in vitro studies on expression of individual genes are inconsistent and difficult to extrapolate to the human thyroid. A prospective single-center study has now demonstrated the importance of human TSH in the differential expression of thyroid-specific genes in vivo.

The authors measured gene expression in both normal and nodular thyroid specimens from 39 patients undergoing thyroidectomy. In 17 patients (Group 1), serum TSH levels were normal and surgery was performed soon after diagnosis. The remaining 22 patients (Group 2) had undergone TSH suppression for ≥6 months, resulting in a TSH level <0.5 mU/l.

In normal tissue from Group 2, levels of sodium–iodine symporter SLC5A5 (NIS) and apical iodide transporter SLC5A8 (AIT) gene expression were lowest and thyroglobulin gene expression was highest. Comparison of normal tissue from the two groups showed reduced transcription of the SLC5A5 and thyroperoxidase genes in Group 2, along with minor reductions in transcription of SLC5A8, thyroglobulin and the transcription factor PAX8. Transcription of the TSH receptor TSHR, transcription factor TTF1 and pendrin SLC26A4 genes was unaltered. After exclusion of patients with malignancy, SLC5A5 mRNA expression was lower in nodular than in normal tissue from Group 1; the same was not seen in Group 2.

Results suggest that TSH is involved in the transcription of most thyroid-specific hormones, with expression of some being completely dependent on its presence. Understanding of the role of TSH might be enhanced through gene-array or proteomic studies.