Thyroid Hormones

What are the two major thyroid hormones?

Thyroxine (T4)( Biggest producer) and triiodothyronine (T3).

Which thyroid hormone is more potent?

T3; about 4× as potent as T4.

What is the main role of T4?

T4 primarily serves as a precursor that is converted to the more active T3 in peripheral tissues.

What is the basic structural unit of the thyroid gland?

The thyroid follicle.

What fills the lumen of a thyroid follicle and its major component?

Colloid.

Major component = Thyroglobulin (TG).

Why is the thyroid unusual among endocrine glands?

It stores large amounts of thyroid hormone precursors extracellularly in the colloid.

What is the orientation of a thyroid follicular cell?

The basal membrane faces the blood/capillaries, while the apical membrane faces the colloid.

What occurs at the apical surface of the follicular cell?

Iodination/organification and endocytosis of thyroglobulin.

What occurs at the basal surface of the follicular cell?

Release of thyroid hormones into the blood.

What is the main dietary source of iodide?

Iodized salt.

What happens to dietary iodide after absorption?

It is well absorbed from the GI tract and enters the bloodstream.

How does NIS transport iodide, what is it driven by?

It cotransports 1 iodide ion with 2 sodium ions across the basolateral membrane. Driven by Na⁺/K⁺-ATPase, which keeps intracellular Na⁺ low.

What is iodide trapping?

The concentration of iodide inside thyroid follicular cells to about 30 times its concentration in the blood.

What is thyroglobulin?

A large glycoprotein synthesized by thyroid follicular cells that is rich in tyrosine residues and serves as the scaffold for thyroid hormone synthesis.

Where is thyroglobulin secreted?

Into the follicular lumen/colloid.

What does pendrin do?

Pendrin transports iodide across the apical membrane of the follicular cell into the colloid.

What enzyme oxidizes iodide (I⁻) into iodine?

Thyroid peroxidase (TPO).

Where is thyroid peroxidase located?

At the apical membrane.

What is organification/iodination?

The covalent attachment of iodine to tyrosine residues on thyroglobulin.

What are MIT and DIT?

MIT = monoiodotyrosine; DIT = diiodotyrosine.

What is coupling in thyroid hormone synthesis?

The combination of iodinated tyrosine residues on thyroglobulin to form thyroid hormones.

What does DIT + DIT produce?

T4 (thyroxine).

What does MIT + DIT produce?

T3 (triiodothyronine).

Where are T3 and T4 stored before secretion?

Still attached to thyroglobulin in the colloid.

Why can symptoms of thyroid hormone deficiency be delayed?

The thyroid has a large stored reserve of iodinated thyroglobulin/hormone, so deficiency effects may not appear for several months after synthesis stops.

How are T3 and T4 released from thyroglobulin?

TSH stimulates endocytosis of iodinated thyroglobulin; vesicles fuse with lysosomes, where proteolysis releases T3 and T4.

What happens to MIT and DIT after thyroglobulin is broken down?

They are deiodinated and recycled.

What enzyme recycles MIT and DIT?

Iodotyrosine deiodinase.

What is the major thyroid hormone carrier protein?

Thyroxine-binding globulin (TBG).

Which thyroid hormone has the longer half-life?

T4, with a half-life of about 6–7 days.

Why does T4 have a longer half-life than T3?

T4 has a higher affinity for TBG, while T3 has a lower affinity.

Which form of thyroid hormone is physiologically active?

Only free, unbound thyroid hormone is physiologically active.

How is T4 activated in target tissues?

T4 is converted to T3 by 5′-iodinase, which removes one iodine from the outer ring.

Why is T3 considered the main active thyroid hormone?

Intracellular thyroid hormone receptors have a high affinity for T3, and T4 primarily serves as its precursor.

What type of receptor do thyroid hormones bind?

Intracellular/nuclear receptors.

What happens after T3 binds its nuclear receptor?

It activates nuclear transcription of genes, leading to synthesis of new proteins and physiologic effects.