Thyroid Hormone Synthesis and Secretion

The thyroid is largely composed of a collection of spherical structures known as follicles. Specialised follicular cells called epithelial cells surround each follicle. Within each follicle is a colloid (a semi-liquid gelatinous substance). The follicular space and the colloid that it contains serve as a reservoir for all the materials required for producing thyroid hormones. It is within each of these thyroid follicles that much of the activity leading to the production of thyroid hormones occurs.

The thyroid gland uses the element iodine in its production of thyroid hormones. Iodine in the diet usually comes in the form of a compound such as sodium iodide or potassium iodide (iodised salt often contains these forms of inorganic iodide).

The epithelial cells surrounding each follicle collect circulating inorganic iodide and through a series of steps this form of iodine is used to create the two thyroid hormones T4 and T3. The steps are essentially:

  1. Transporting the iodide into the thyroid epithelial cells. The rate of follicular transport of iodide appears to speed up with higher levels of TSH.
  2. A protein called thyroglobulin (Tg) is produced within the thyroid epithelial cells. Thyroglobulin is a large complex protein, which is used to hold the majority of the iodine concentrated in the thyroid. Thyroglobulin is made from an amino acid residue called tyrosyl, which is made using the amino acid tyrosine.
  3. The thyroglobulin protein is released by the epithelial cells, which surround each thyroid follicle into the colloid within each follicle. It is within this colloid that a lot of the action occurs.
  4. An enzyme called thyroid peroxidase (TPO) is also made with the thyroid epithelial cells and this enzyme is also released into the colloid within the follicle.
  5. Within the colloidal substance iodotyrosine molecules within thyroglobulin protein are joined with the help of the enzyme thyroid peroxidase (TPO). An iodine atom is added with tyrosine to make mono-iodotyrosine (T1). Two iodine atoms are also combined with tyrosine to make di-iodotyrosine (T2). T1 and T2 are combined with the help of TPO to make T4 and T3 (the two iodothyronines).
  6. The thyroglobulin protein is therefore altered through these processes. The thyroglobulin protein now holds the T1, T2, T3 and T4 inert within its structure.
  7. Thyroglobulin contained within a little of the colloid has to move back from the main body of the colloid within the follicle and into the thyroid follicle epithelial cells.
  8. Once within the epithelial cells, the free iodotyrosines (T1 and T2) and iodothyronines (T3 and T4) may be released from the complex thyroglobulin protein that they are still a part of. Specialised enzymes break down the thyroglobulin and release the separate T1, T2, T3, and T4 from the thyroglobulin protein.
  9. The thyroid hormones remain as part of the thyroglobulin (Tg) protein until the thyroid is ready to secrete them, via the stimulation of TSH.
  10. When the thyroid is asked to produce thyroid hormones through the stimulation of TSH several things happen:
  11. Enzymes break some of the T1 and T2 down and the iodide is reused and released back into the colloid as new thyroglobulin.
  12. T4 and T3 diffuse with some T1 and T2 through the epithelial cells of the thyroid and into the bloodstream.

 

It can be seen from the above that the thyroid follicles act as a factory and a warehouse for thyroid hormones.

TSH has an effect on all phases of the use of iodine within the thyroid gland. It is a fairly complex process and a small wonder that it works at all!