THYROID HORMONES

By

Saleh Sharif
Include triiodothyronine (T3) and tetraiodothyronine (thyroxine; T4)

Are synthesized as part of a very large precursor molecule (thyroglobulin)

They are stored in an intracellular reservoir (colloid)

There is peripheral conversion of T4 to T3 (much more active)

 Thyroglobulin

The precursor of T4 and T3

Iodinated, glycosylated protein

Is composed of two large subunits

Contains 115 tyrosine residues (potential site of iodination)

70% of the iodide in thyroglobulin exists in the inactive precursors,

monoiodotyrosine (MIT) and diiodotyrosine (DIT)

30% is in the iodothyronyl residues, T4 and T3

When iodine supplies are sufficient, the T4 : T3 ratio is about 7:1

Required for tyrosyl coupling and iodide organification

 Synthesis

Synthesized in the basal portion of the cell and moves to the lumen

Storage form of T4 and T3 in the colloid

Several weeks’ supply of these hormones exist in the normal thyroid

Upon TSH secretion, colloid reenters the cell via phagocytosis

Various acid proteases and peptidases hydrolyze the thyroglobulin and

release T4 and T3
 Iodide metabolism

Thyroid is able to concentrate I− against a strong electrochemical gradient

Linked to the Na + -K + ATPase-dependent thyroidal I− transporter

Thyroid to iodide in serum (T:S ratio) is a reflection of the activity of the

transporter.

T:S ratio in humans on a normal iodine diet is about 25:1.

Thyroid is the only tissue that can oxidize I− to a higher valence state

This step involves a heme-containing peroxidase

Thyroperoxidase requires hydrogen peroxide as an oxidizing agent

H2O2 is produced by an NADPH-dependent enzyme resembling

cytochrome c reductase

Antithyroid thiourea drugs

 Synthesis

Coupling of two DIT molecules to form T4

MIT and DIT to form T3

Deiodinase removes I− from the inactive mono and diiodothyronine

molecules in the thyroid

This mechanism provides a substantial amount of the I− used in T4 and T3

biosynthesis

Peripheral deiodinase in target tissues such as pituitary, kidney, and liver

selectively removes I− from the 5′ position of T4 to make T3