Thyroglobulin: A master regulator of follicular function via transcriptional suppression of thyroid specific genes

lumen, is a potent regulator of follicular physiological concentrations of TG significantly suppress thyroid-specific gene expression in cultured thyr ocytes and antagonizes the maximal negative feedback function. Thus, Thyroi d gland function is thought to be tightly regulated by thyrotropin (TSH). H owever, the function of each thyroid follicle is heterogeneous despite havi ng the same blood supply of TSH and despite homogeneous thyrocyte expressio n of the TSH receptor (TSHR). The nature of this heterogeneity is not fully understood. Recent studies showed that thyroglobulin (TG) protein, stored in the follicular TSH stimulation of thyroid-specific genes: thyroglobulin, thyroid peroxidase, sodium iodide symporter and TSH receptor. In vivo stud ies are consistent with these results. This regulation is mediated by TG su ppression of thyroid-specific transcription factors: thyroid-transcription factors 1 and 2 as well as Pax-8. We propose a model of follicular activity wherein each follicle has its own cycle of thyroid hormone synthesis and s ecretion and wherein follicular heterogeneity reflects the asynchronous fun ction of individual follicles. We provide evidence that this mechanism may be related to the phenotype of some thyroid diseases.