Thyroid gland: Histology and Hormones

• An endocrine gland situated at the root of the neck, one on either side of the trachea.
• Bi-lobed, connected to each other by an isthmus.
• Weight is about 20-40gm, 4 to 4.8 x 1 to 1.8 x 0.8 to 1.6 cm in size, in adults.
• Larger in females as compared to males.
• Changes occur in structure and function in different stages of sexual cycles in females.
• Pregnancy and lactation increases its function slightly.
• In menopause, its function declines.

Image source: biologynotes

Histology of Thyroid gland

• Contains large number of closed follicles lined with cuboidal epithelial cells.
• So the cells are called follicular cells.
• Thyroglobulin, a colloidal substance, is secreted by these follicular cells.
• This substance fills the follicular cavity.
• Tetra-iodothyronine (T4 or thyroxine) and tri-iodothyronine (T3) are also secreted by these cells.
• Parafollicular cells present in between follicles which secretes calcitonin.

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Hormones of Thyroid gland

• T4, T3 and calcitonin are the main hormones secreted.
• T4 also called thyroxine forms about 90% of secretion.
• T3 forms only 9-10% of total secretion.
• T4 and T3 are derivatives of amino-acids tyrosine which contains iodine.
• T3 has four times more potency than T4 though T3 acts for shorter period than T4.
• T4 has more affinity and binds strongly with plasma proteins so released slowly and acts longer.
• T3 has less affinity with plasma proteins and binds loosely, so released quickly and acts shorter.
• Therefore, T4 acts slowly on the target cells than T3.
• T4 has half-life of 7 days which is longer than in T3 i.e. T3 has between 10 and 24 hours.
• T4 is secreted more i.e., 80-90 μgm/day whereas T3 is 4-5 μgm/day.
• Reverse T3 is secreted only about 1-2 μgm/day.
• Plasma level of T4 is more i.e., 8 μgm/dl whereas T3 is 0.12 μgm/dl.
• In muscles, liver and kidney, thyroid hormones generally degrades.

Thyroid Hormones Synthesis

• In thyroglobulin present in follicular cavity, thyroid hormones synthesis occurs.
• Iodine and tyrosine from diet absorbed from GI tract, are essential materials for its formation.
• Iodine is converted to iodide.
• 1mg of iodine per week or about 50 mg/year iodine is required.
• Salt is iodized with one part of sodium iodide to every 100,000 parts of sodium chloride to prevent iodine deficiency.
• In five stages, synthesis of these hormones occurs. They are:

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a) Thyroglobulin synthesis

• Thyroglobulin is secreted by ER and golgi apparatus of the follicular cells continuously.
• Each thyroglobulin molecule contains 140 molecules of amino acid tyrosine.
• Thyroglobulin is stored in the follicle after synthesis which is a large glycoprotein.

b) Iodide trapping

• From blood, iodide is carried to follicular cell against electrochemical gradient.
• This process is known as iodide trapping.
• Sodium-iodine symport pump helps to transport iodide along with sodium.
• This pump is also called iodide pump.
• Iodide is 30 times more concentrated in thyroid than in blood.
• Hyperactivity of thyroid gland increases iodide concentration by more than 200 times.

c) Iodide oxidation

• Iodine is required to combine with tyrosine to form thyroid hormones.
• So iodide is oxidized to form iodine which is the elemental form.
• This oxidation process occurs in follicular cells.
• It occurs in presence of thyroid peroxidase.
• This enzyme absence or inactivity stops thyroid hormones formation.

d) Transport of iodine to follicular cavity

• Iodine is transported to follicular cavity later on by an iodide-chloride pump.
• This pump is also called pendrin.

e) Iodination of Tyrosine

• Iodination means combination of iodine with tyrosine.
• It occurs in thyroglobulin.
• Iodine is first carried to follicular cells into the follicular cavity.
• In this cavity, iodine binds with thyroglobulin.
• This process is called organification of thyroglobulin.
• Tyrosine present in the thyroglobulin then combines with iodine.
• Iodinase enzyme secreted by follicular cells accelerates this iodination process.
• This process occurs in different stages.
• Firstly, monoiodotyrosine (MIT) is formed which later converted to diiodotyrosine.
• MIT and DIT are also known as iodotyrosine residues.

f) Coupling reactions

• The above residues get coupled with each other.
• Coupling occurs in different configurations to give different thyroid hormones.
• Coupling reactions includes following steps:

i) One molecule MIT and one molecule of DIT forms tri-iodothyronine(T3).

ii) Sometime the above reaction yields another form of T3 called reverse T3 or rT3.

iii) This form of T3 is 1% of thyroid output.

iv) Two molecules of DIT form tetra-iodothyronine which is also called thyroxine.

Storage of thyroid Hormones

• Remains in the form of vesicles within thyroglobulin.
• Stored here in this form for longer period.
• 5-6 molecules of thyroxine are present in each thyroglobulin molecule.
• In average, 1 triiodothyronine molecule is present for every 10 molecules of thyroxine.
• In combination form, the thyroid hormones can be stored for long time i.e., for several months.
• This is the only endocrine gland for storing hormones for about 4 months.
• Signs and symptoms of deficiency to these hormones, do not appear for about 4 months though synthesis of hormones stops.

References:

i) https://www.ncbi.nlm.nih.gov/books/NBK551659/

ii) https://www.uptodate.com/contents/image?imageKey=ENDO%2F76931

iii) https://www.biosciencenotes.com/thyroid-gland-and-thyroid-hormones/

iv) https://www.simplepharmanotes.com/2021/08/thyroid-gland.html

Thyroid gland: Histology and Hormones