Thyroid Hormones

Author: Gianpiero Pescarmona
Date: 06/01/2012



Active transport of iodide into the thyroid gland is a crucial and rate-limiting step in the biosynthesis of thyroid hormones. It is mediated by a specific sodium-dependent iodide transporter located at the basolateral membrane of thyroid follicular cells, the sodium iodide symporter - NIS.

sodium iodide symporter - NIS.

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NIS gene mutations

Iodide transport defects resulting in congenital hypothyroidism are suggestive of a defective NIS molecule due to NIS gene mutations. Diagnostic criteria for an iodide transport defect are: 1) goiter with hypothyroidism or compensated hypothyroidism, 2) little if any uptake of radioiodine, 3) no concentration of iodide by salivary glands


When relevant for the function

  • Primary structure
  • Secondary structure
  • Tertiary structure
  • Quaternary structure

Protein Aminoacids Percentage
The Protein Aminoacids Percentage gives useful information on the local environment and the metabolic status of the cell (starvation, lack of essential AA, hypoxia)

Protein Aminoacids Percentage (Width 700 px)


mRNA synthesis
protein synthesis

post-translational modifications


cellular localization,
biological function

  • Enzymes
BRENDA - The Comprehensive Enzyme Information System"URL":
KEGG Pathways"URL":
Human Metabolome Database"URL":
  • Cell signaling and Ligand transport
  • Structural proteins


Pituitary-derived TSH had been known for decades to stimulate iodide transport into the thyroid gland via the adenylate cyclase cAMP pathway

Exposure to T3 and dexamethasone suppressed iodide accumulation, and expression of NIS mRNA and protein
Treatment with tRA significantly stimulated NIS mRNA as well as NIS protein expression, but it is cell selective.
Adenosine has been reported to stimulate NIS mRNA and protein expression

Smoking Reduces Iodine Transport Into Breast Milk

Valproic acid induced NIS gene expression, NIS membrane localization, and iodide accumulation in NPA cells, and it was effective at clinically safe doses in the therapeutic range. In ARO cells, only induction of NIS mRNA was observed, and was not followed by any change in iodide uptake. The authors concluded that valproic acid is effective at restoring the ability of NPA cells to accumulate iodide.

The iodine metabolism according to L. Fugazzola -

Redox up-regulated expression of rat liver manganese superoxide dismutase and Bcl-2 by thyroid hormone is associated with inhibitor of κB-α phosphorylation and nuclear factor-κB activation
Fernandez V;
2005, Volume: 186(3) Page(s): 539-547


Mammary gland NIS and its clinical implications

NIS mRNA and protein expression has been reported in a variety of extrathyroidal tissues, including salivary and lacrimal glands, gastric mucosa, kidney, placenta and mammary gland suggesting that iodide transport in these tissues is mediated by the expression of functional NIS protein. In the lactating mammary gland iodide is actively transported and secreted into the milk, thereby supplying iodide to the infant for the biosynthesis of thyroid hormones which are essential for the development of the nervous system, skeletal muscle and lung

Examination of mgNIS protein expression at various physiological stages showed that mgNIS is exclusively present in the mammary gland during gestation and lactation, in contrast to the constitutive expression of NIS in the thyroid gland. It depends on HCG? + estrogen, prolactin and oxytocin. )

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