INDG 401 Lecture Notes - Lecture 9: Thyroid Hormones, Thyroid, Iodine Deficiency
9 Jun 2018
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Lecture 10
➢ Thyroid Gland
o Organ (15-20 g) specialized for endocrine hormone
production has butterfly shape & located below larynx
o Large blood supply innervated by sympathetic nerves
o In addition to releasing thyroid hormones, the thyroid
glands have parathyroid glands embedded within,
involved in calcium metabolism along with the C-cells.
o C-cells are embedded within the thyroid
▪ Thyroid gland, parathyroid gland, C-cells
➢ Histology of the Thyroid Gland
o Functional units are thyroid follicles consisting
of a single layer of epithelial cells surrounding
a lumen that contains colloid → several 1000
follicles per gland
o Post-ganglionic sympathetic nerves control the
blood flow through the gland
▪ The blood flow regulates the T4/T3
release by affecting the delivery of
TSH, iodine and nutrients
o The substances secreted into the center are very
greasy. The hormones can be stored within the
follicles. T3 and T4 are lipophilic.
o The thyroid hormones (lipophilic) may be
STORED within the colloidal mass of the
follicle. Even if it is a lipophilic hormone, we
can maintain a large supply of T4 and T3 over a
long period of time. There is enough storage of
T4 and T3 to last 7 weeks (hypothyroidism would occur late).
o Hyperactive - producing too much (expansion of the follicles, but LESS colloid) —> goiter
o Hypoactive state (expansion) —> loiter
C-cells are also associated with the follicles. They are contained within the wall of the follicles.
The parathyroids are discrete molecules, which form their own glands.
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➢ Structure of T4, T3 and its metabolites
o T4 and T3 are the 2 biologically active forms
o rT3 and T2, the inactive forms, are formed in
the peripheral tissues
o T4 and T3 are formed from tyrosine being
iodinated, which may occur in one (mono-)
or two (di-) locations.
o Deiodinating T3 → T2
o Deiodinating T4 → T3
o Deiodination occurs when there is an excess
of T3 and T4
➢ Synthesis of T4 and T3 requires 6 steps
o 1. Active transport of iodine in the thyroid cell from the
extracellular fluid → “trapping”
o 2. Oxidation of iodide to iodine and iodination of tyrosyl residues in
thyroglobulin → organification
o 3. Linking pairs of iodotyrosine in thyroglobulin to form T3 and T4
→ coupling
o 4. Proteolysis of TG to release T3 and T4
o 5. Deiodination of iodotyrosines in thyroid cell and recycling of I
o 6. Intrathyroidal 5’-deiodination of T4 to T3 (conversion)
o Tyroid hormone synthesis requires that NIS (NA+/I- symporter, TG
(thyroiglobulin) sodium/iodide symporter, TPO (tyroid perodixase)
be present, functional and uninhibited -
o A signal from the hypothalamus produces TRH to stimulate the pituitary to produce TSH. TSH is
then released and travels to the thyroid gland to stimulate T3 and T4 production and release.
Cells have Gs and Gq GPCR
Iodide from the extracellular fluid is actively transported into
the cell, reaching the apical membrane where a colloid is
located. Thyroid peroxidase, TPO, and thyroglobulin are
produced by the activation of the TSH receptor. TPO can then
link iodides onto the molecules, and also act to couple MIT
and DIT on the thyroglobulin molecules itself. TSH is also
stimulating pinocytosis of the compound, bringing it back to
the cytoplasm, where lysosomes act on it and proteolytically
break down the protein into its amino acids, releasing T3 and
T4 to be carried by the bloodstream.
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➢ NIS (Na/I symporter) stimulated by TSH
o Transport of iodine against a steep concentration gradient
▪ Iodine concentration in the blood plasma is extremely low
▪ 30-40-fold difference between ECF and cytoplasm
o iodine transport is via a symport
▪ co-transport of Na+ and I- driven by
the Na+ gradient
▪ Na+ gradient is maintained by the ATP
Na+/K+ pump
• i.e. requires energy input
▪ Additional ATP requiring pumps may
be present
o Active uptake of iodide in symport with
sodium, along with a sodium ATPase pump, to
bring the sodium back out (balancing the sodium concentration
o Pharmaceutical products may inhibit the reaction with TPO, which may inhibit the
overproduction of T3 and T4, blocking iodination of the thyroglobulin.
o Negative anions in the extracellular fluid block the active transport of iodine.
➢ Inhibitory anions
o The symporter system may be blocked by negative anions.
o Anions (such as CIO4- block uptake of iodine
o Perchlorate can be used to block hyperthyroidism
▪ Also environmental inhibitor of thyroid
o Radioactive iodine (oral I131) can be used to destroy thyroid tissue
▪ In case of cancer or hyperthyroidism
o Bromide (Br-) and nitrite (NO2-) are competitive inhibitors
▪ Present in the diet
▪ Causes apparent iodine deficiency in some areas of the world
o Takes advantage of the symport to bioaccumulate radioactive iodine, which will destroy thyroid
tissue, killing the tissue from the inside-out.
o I^131 has a short half-life, allowing it to clear from our system rapidly while still using it as a
non-surgical method to destroy thyroid tissue.
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Tsh, iodine and nutrients: the substances secreted into the center are very greasy. The hormones can be stored within the follicles. T3 and t4 are lipophilic: the thyroid hormones (lipophilic) may be. Stored within the colloidal mass of the follicle. Even if it is a lipophilic hormone, we can maintain a large supply of t4 and t3 over a long period of time. T4 and t3 to last 7 weeks (hypothyroidism would occur late): hyperactive - producing too much (expansion of the follicles, but less colloid) > goiter, hypoactive state (expansion) > loiter. They are contained within the wall of the follicles. The parathyroids are discrete molecules, which form their own glands. Synthesis of t4 and t3 requires 6 steps: 1. Active transport of iodine in the thyroid cell from the extracellular fluid trapping : 2. Oxidation of iodide to iodine and iodination of tyrosyl residues in thyroglobulin organification: 3.
