MECH 430 Lecture Notes - Lecture 9: Thyroid, Iodine Deficiency, Reverse Triiodothyronine
9 Jun 2018
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Lecture 8
➢ 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 producing thyroid hormones, there are also
parathyroid glands that are involved in Ca function
o Parathyroid glands are embedded in the thyroid gland
➢ 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
▪ In the lumen, we produce our thyroid hormone and
keep them bound to a protein that is heavily
glycosylated
o Ability to store this lipophile in the center of the ball
(colloidal mass) of cells → therefore you can maintain a
large supply of T3 and T4 over time to last about 7 weeks,
therefore if the synthesis is cut off, you will have adequate
levels stored before you experience hypothyroidism
o Post-ganglionic sympathetic nerves control the blood flow through the gland
▪ The blood flow regulates the T4/T3 (lipophilic) release by affecting the delivery of TSH,
iodine and nutrients
▪ These follicles expand during inactivity or over active and producing too much T3 → you
see a goiter appear around the neck area
➢ 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 tyrosine being iodinate to get a monoiodotyroisine
o if you combine 2 diiodotyrosine, you get a thyroxine (T4)
o if we diodinate T4, we get reverse T3 by removing one of the iodine → you get the reverse of
what a T3 molecule looks like
o **remember where the iodine is and the simple structure, particularly the red box **
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o T3 has a more bioactive activity than T4, therefore we rely on it more
o Excess T4 that is not needed is converted from T4 to T2 or T3
➢ Synthesis of T4 and T3 requires 6 steps
o when TSH stimulates the thyroid gland, there are 6 steps that leads
to the release of T4 and T3
o 1. Active transport of iodine in the thyroid cell → “trapping”
o 2. Oxidation of iodide 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 → take back into cell by
endocytosis to digest the protein away to release the T3 and T4
o 5. Deiodination of iodotyrosines in thyroid cell and recycling of I
→ iodine will be reused to make new T4 and T3
o 6. Intrathyroidal 5’-deiodination of T4 to T3 → remove an iodine to revert a T4 to a T3
o Tyroid hormone synthesis requires that NIS (NA+/I- symporter, TG (thyroiglobulin), TPO
(tyroid perodixase) be present, functional and uninhibited
▪ If something goes wrong with any of these functions, including thyrosine binding to its
receptor will result in disregulation
o **know the pathway on the right well**
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• Increase in cAMP will stimulate the cell to increase
the cell size and number, and follicle formation
• For synthesis of thyroid hormones, we increase the
trapping of iodine
• We also increase the oxidation of glucose and the
generation of NADPH that is required for our
oxidation reactions
• Remember that iodine
come from the
extracellular fluid
• Summary of
everything explained
above →
• when you have
proteolysis, there is
release of the amino
acids and its
constituents to release
the T3 and T4
➢ 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
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