Iodine uptake is a result of an active transport mechanism mediated by the NIS protein, which is found in the basolateral membrane of thyroid follicular cells.

As a result of this active transport, iodide concentration inside follicular cells of thyroid tissue is 20 to 50 times higher than in the plasma.

[13] Once inside the follicular cells, the iodide diffuses to the apical membrane, where it is metabolically oxidized through the action of thyroid peroxidase to iodinium (I+) which in turn iodinates tyrosine residues of the thyroglobulin proteins in the follicle colloid.

[15][16] NIS expression in the mammary glands is quite a relevant fact since the regulation of iodide absorption and its presence in the breast milk is the main source of iodine for a newborn.

Note that the regulation of NIS expression in thyroid is done by the thyroid-stimulating hormone (TSH), whereas in breast is done by a combination of three molecules: prolactin, oxytocin and β-estradiol.

TSH first binds to its receptors which are joined to G proteins, and then induces the activation of the enzyme adenylate cyclase, which will raise the intracellular levels of cAMP.

The TSH can also regulate the iodide uptake at a posttranslational level, since, if it's absent, the NIS can be resorted from the basolateral membrane of the cell in to the cytoplasm where it is no longer functional.

[29] There is also a connection between the V600E mutation of the BRAF oncogene and papillary thyroid cancer that cannot concentrate iodine into its follicular cells.

[31] One of these therapies is based on transferring NIS in cancer cells of different origin (breast, colon, prostate...) using adenoviruses or retroviruses (viral vectors).