Thyroid Flashcards
When stimulated by TSH, what does the thyroid gland do in general?
The thyroid gland uses iodine to produce thyroid hormones (T3 and T4) which would increase the metabolic rate and influence growth and development.
Functional unit of the thyroid gland?
Thyroid follicle
- 1 layer of follicular epithelium
- filled with colloid which contains your thyroglobulin, a protein containing tyrosyl groups which will be iodinated to from the THs)
What are parafollicular cells? Other names? Function
Parafollicular cells/C cells
-Produce calcitonin which is important for Ca2+ and Phosphate balance
What are the thyroid hormones? Compare in terms of 1. Name 2. Diff in structure 2. Activity 3. %secretion
T4 Aka thyroxine T4 because it has 4 iodine atoms A prohormone (so by itself, not very active; has some activity but it is not the one responsible for most of the effects of thyroid hormone) Comprises 90% of TH secretion Converted in peripheral tissues to T3 T3 Active form Aka Triiodothyronine Has 3 iodine atoms 10% of thyroid hormone secretion Sir’s mnemonics: “Three triumphs where four fails” 3 = active 4 = prohormone, not v active, will fail in doing the thyroid thing rT3 Aka reverse T3 Inactive Another form of prohormone The iodine arrangement is different
Synthesis and secretion of thyroid hormones?
- Trapping
>Put I- from blood into the thyroid follicle (follicular cell) through Na+-I-symporter (NIS), an active transporter
>NIS is more active if the dietary I- intake is low
>For every 2 Na+ that enters, 1 I- enters - Transport and oxidation of I-
>Transport iodide from follicular cell into the colloid through Pendrin (transporter)
>Once inside the colloid, it becomes oxidized to iodine by thyroid peroxidase (TPO)
>TG is also produced in the follicular cells and gets transported into the colloid through exocytosis. - Iodination of TG
>Tyrosyl residues of the TG will be iodinated (For each tyrosyl reside, 1-2 iodine will be incorporated to its structure)
>This process is also known as ORGANIFICATION - Conjugation of iodinated tyrosyl
>Combination of iodinated tyrosyl residues
>2 iodinated tyrosyl will combine to form 1 iodothyronine
>Catalyzed by TPO - Endocytosis, Proteolysis, & Release
>The TH stuck inside the colloid is still connected to thyroglobulin so:
TG will go back to the follicular cell via endocytosis -> it will fuse tih lysosome -> The lysosomal digestive enzymes degrade TG and the THs are now released from your TG and they can now be secreted.
T or F. The difference between the concentration of free T3 and T4 is 9 fold?
No!!! T4 is 90% of the secretion but it is protein-bound more than T3 so the free T4 is only 2-3 x higher than T3.
Importance of protein-bound form?
- Can’t perform its effects (like inactive)
- It extends the half-life
- Maintains a large circulating reservoir of TH
What transports T4 to the CNS?
Transthyretin (impt bc CNS has a BBB)
What is a deiodinase? Fxn?
So what now happens to T3 and T4?
Before it does its fxn, you would want to convert T4 to its more active form, T3, by deiodinases (means it removes an iodine)
Type 1 deiodinase (D1)
Occurs in high concentrations in the cell membrane of the liver, kidneys, and thyroid
Since this deiodinase is mainly in the CM, it supplies circulating T3 in plasma
Why do we need circulating T3? Because not all cells have a high expression of these deiodinases, some cells don’t so they would depend on the deiodinases of other cells to supply them with the T3 hormone
Thus it explains why this deiodinase is found in the liver and kidneys. These two organs receive a lot of blood supply so they can help supply T3 to other tissues.
Type 2 deiodinase (D2)
Occurs in the ER of the ms, CNS, pituitary, placenta, brown fat, and some other cells
So it’s more impt for feedback inhibition (since found in CNA and pituitary)
Deiodinase that converts T4 to T3 in your CNS, pituitary so it’s the one that helps inform your pituitary that there’s too much T3 or less TH
Supplies intracellular T3
Impt for feedback inhibition of TSH release
Type 3 deiodinase (D3)
Converts T4 to rT3 (inactivating!)
Inactivating kind of deiodinase
Increased during hyperthyroidism to counteract those THs
Impt in the degradation or elimination of your THs bc it is inactivating
Once you’ve converted much of your T4 to T3,
THs are transported across PM
In some books, they’d say diffuse across the membrane
But in some books, there are transporters that are involved in bringing them through the membrane
-So they would be transported across your PM and once they get inside, your T3 would bind to thyroid hormone receptor (complex with Retinoid X Receptor (RXR) and they are attached to or they will affect your gene transcription
And ofc if you affect gene transcription, you affect expression of certain DNA or synthesis of proteins
So TH has a lot of effects bc it modifies the DNA/gene transcription
Activate NRs to alters gene transcription
Your thyroid hormone receptor has ~x10 greater affinity for T3
Thus, T3 is the more active hormone bc THr prefers it
90% of THr will be occupied by T3; so only 10% will receive your T4
Also has nongenomic effects
More recent research
But so far, this gene transcription pathway is the major effect of your thyroid hormone
Effect of increased TH lvls on
- BMR
- Carb metabolism
- Protein metabolism
- Lipid metabolism
- Thermogenesis
- ANS
Table
Effect on Different Organs
- CV (incl BP)
- Respi
- Skeletal ms
- Bone & CTs
- CNS
- Repro & Endocrine
Table
Regulation
> Hypothalamus produces TRH -> stim TSH release from AP
TSH has a lot of fx w/ regards to TH (Stimulates every aspect of thyroid fxn; increases all steps of TH synthesis)
TSH also promotes hypertrophy and hyperplasia of follicular cells
> Free T3 and T4 inhibit TRH and TSH release (relatively slow process)
Effect of somatostatin and dopamine on TSH secretion?
Inhibitory
What is the Wolff-Chaikoff effect
Xs iodide (intake) -> Suppress TPO activit -> less TH synthesis
*Pero overtime may adaptation, di pwedeng forever suppressed so eventually NIS expression will be reduced = less iodide trapping and less inactivation of TPO and TH synthesis will resume w/in days to weeks
