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Endocrinology ; 140(11): 5422-30, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10537174

ABSTRACT

A major function of the thyrocyte is to take up and concentrate iodide. This is needed for thyroid hormone synthesis and is accomplished by the sodium iodide symporter (NIS), whose expression and activity are up-regulated by TSH. Recently, we reported that follicular thyroglobulin (TG) is a potent suppressor ofthyroid-specific gene expression and can overcome TSH-increased gene expression. We suggested this might be a negative feedback, autoregulatory mechanism that counterbalanced TSH stimulation of follicular function. In this report, we support this hypothesis by coordinately evaluating TG regulation of NIS gene expression and iodide transport. We show that physiological concentrations of TG similarly and significantly suppress TSH-increased NIS promoter activity, NIS protein, and NIS-dependent iodide uptake as well as RNA levels. We show, in vivo, that TG accumulation at the apical membrane of a thyrocyte facing the follicular lumen is associated with decreased uptake ofradioiodide. It is likely, therefore, that TG suppresses NIS-dependent iodide uptake and NIS gene expression in vivo, as is the case in vitro. RNA levels of NIS and vascular endothelial growth factor/vascular permeability factor, which has been reported to be TSH regulated and possibly associated with TSH-increased iodide uptake, are coordinately decreased by follicular TG as a function of concentration and time. Also, removal of follicular TG from the medium, but not TSH, coordinately returns NIS and vascular endothelial growth factor/vascular permeability factor RNA levels to their TSH-stimulated state. TG accumulated in the follicular lumen appears, therefore, to be a negative feedback regulator of critical TSH-increased follicular functions, iodide uptake, and vascular permeability.


Subject(s)
Carrier Proteins/genetics , Gene Expression/drug effects , Iodides/metabolism , Membrane Proteins/genetics , Symporters , Thyroglobulin/pharmacology , Thyroid Gland/metabolism , Animals , Cell Line , Cell Membrane/metabolism , Endothelial Growth Factors/genetics , Iodine Radioisotopes/metabolism , Lymphokines/genetics , Promoter Regions, Genetic , RNA/metabolism , RNA, Messenger/metabolism , Rats , Thyroglobulin/metabolism , Thyroid Gland/drug effects , Thyrotropin/pharmacology , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
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