Thyroid Gland Flashcards
What does the thyroid gland produce?
what is the functional unit of the thyroid gland? what is it surrounded in?
where’s the lumen of the thyroid gland?
produces prohormone tetraiodothyronine (T4) and the active hormone triiodothyronine (T3)
Thyroid follicle –> surrounded by a single layer of epithelial cells
in the follicle called “colloid”
Of T3 and T4, which one is active?
T3 –> this one is the most active and biologically relevant.
What cells are seen in the thyroid?
C cells –> which produce calcitonin!
C cells are also called “parafollicular cells”
What is colloid have inside it?
what stimulates this colloid to release stuff?
newly synthesized thyroid hormones attached to the thyroglobulin.
so an internal pool of thyroid pool.
TSH!
How do we get to produce T4 and T3?
How does it start from circulation?
What’s the difference between the two products?
what’s to note about these two initial products? (differences and activity)
What combination of these creates T3 or T4?
2 Iodide(I-) (trapped from circulation) + H2O2 –> Iodine (I2)
Iodine + Tyrosine –> MIT and DIT.. the only difference is the location of the iodine molecule on the molecule (this happens in the thyroglobulin)
MIT and DIT is NOT biologically active.
MIT has only 1 Iodine, DIT has 2 iodine.
depending on the conjugation of those molecules we’re generating either T3 or T4.
2 DIT –> T4
1 DIT + 1 MIT –> T3
What’s to note about the structure of T4 vs T3?
T4 has 4 Iodine ions off of it, or (2 on each benzene ring)
T3 has one Iodine on 1 (outer) ring, and 2 on the inner ring
What is the major secretory product of the TSH?
of T3 and T4, which one usually free?
T4… even though it’s not biologically active! (T4 can be conjugated to T3)
T3.
What are the relative levels of T3/T4?
around 90% of the thyroid hormone is going to be the T4.. 10% is T3, and then there’s going to be 1% of “reverse T3”.
The reverse T3 is the inner ring having only one iodine rather the outer… this is the INACTIVE form of T3.
What can happen to T4?
what enzyme does most of the peripheral conversion? where is it found?
What about the other one?
it can be converted!
80-90% of the conversion of T4-T3 is going to be happening peripherally.
the enzyme that’s doing this is the Deiodinases type 1 –> this does most of the conversion. (found on skeletal muscle)
Deiodinases 2 is going to be localized in the brain in the anterior pituitary –> adds another sensor for T3 levels, which helps put breaks on TSH and this deiodinase is unaffected by starvation
what’s the importance of Deiodinase 2 in the brain?
It can help tell the brain to stop sending out TSH. It will not be affected by starvation.
also if the body is in starvation, it won’t be taken up at all by starving cells so it can still regulate even in starvation.
in starvation, do we want the thyroid to be activating metabolic stuff, oxygen consumption?
so what happens to the T4?
what catalyzes this then?
no. we don’t want to affect the brain so that’s done by shifting to create more of the reverse T3 which is INACTIVE, than the active T3.
this is catalyzed by Deiodinase type 3.
Fasting, Medical and surgical stress, catabolic disease… what do these have in common with the thyroid?
you’re going to have a reduction of conversion of T4 into T3 because you don’t want T3 affecting basal metabolism, heat, or anything like that.
What is on the basolateral membrane of the follicular epithelial cells of the thyroid??
So you have the follicular epithelial cells
on the basolateral membrane:
Na/K ATPase –> keeping the concentration gradient going
“I Trap” –> it’s a symporter called NIS that sends iodide into the cell at the expense of sending 2 Na into the cell, which is going with the gradient.. but the Iodine is going against the gradient.
How is Thyroglobulin synthesized?
what’s on the thyroglobulin?
what happens once iodide is in the follicular cell?.. what is this site called?
What catalyzes the Iodide to Iodine? Where is this happening?
What happens once you have Iodine?
Final step before thyroglobulin can move around freely in the colloid region?
it’s formed in the rough ER, processed by the golgi, and secreted into the lumen.
Thyroglobulin has several molecules of tyrosine and some of those are going to be iodized.
So once the Iodide is in the cell, it’ll be exported through a transporter in the luminal site called “Pendrin”
Within the membrane of the luminal membrane we have peroxidase (TPO).. this is important for catalyzing Iodide to Iodine. (all this is happening as it goes through the luminal (apical) membrane.
This peroxidase also helps catalyze the iodine into MIT and DIT and helps put it on the Thyroglobulin.
Finally, peroxidase helps the conjugation of MIT and DIT to either T3 or T4. (NOTE.. YOU WILL STILL HAVE EXTRA MIT/DIT.. IT’S GOING TO BE RECYCLED)
What happens when you have the completed Thyroglobulin molecule out in the lumen.. how does it get back into the follicular cell and what happens?
what happens to the leftover MIT/DIT?
What’s on thyroglobulin usually? just in general
There is Pinocytosis then of the TG with bounded stuff on it.
then you’ll have lysosomal proteases that breaks the thyroglobulin into different components… T3 and T4 are going to be cleaved into circulation (by proteases of lysosomes), and MIT and DIT are going to be recycled.
MIT and DIT (on the thyroglobulin) are going to recycle the MIT And DIT through “Intrathyroidal deiodinase”!
T3, T4, MIT, DIT.. you can have multiple of each
Through the entire synthesis of. thyroid hormones… what’s going to mediate most of the steps?
what specific step in the pathway is it most typically seen (in her slide)
what’s to note about this and growth? what happens if we have excess TSH
TSH!
pinocytosis of the Thyroglobulin (with T3+T4 bound).
TSH is a growth factor, so when we have excess of this around, the thyroid gland will tend to be enlarged –> goiter.
What happens if we have a deficiency of intrathyroidal deiodinase?
what happens if we don’t have iodide? What’s favored?
what about too much iodide?
it can mimic dietary Iodide deficiency in our diet.. so it’s important to have it intracellularly! because it’s not able to get rid of iodine off of the MIT/DIT, so no iodide can even come through.
T3 is favored
too much? prevent too much thyroid hormone… T4 or reverse T3.
What is the Wolff-Chaikoff effect?
what’s being effected?
inhibiting peroxidase (TPO), which will decrease the production of thyroid hormone.
this is happening due to high levels of Iodide which inhibit organification (abundance of iodide is going to inhibit MIT and DIT production..
its not permanent, it’s transient!!
What different ions competitively inhibiting the Na/Iodide symporter?
Perchlorate… Thiocynate
these alter Thyroid hormone creation.
no iodide coming in, affecting thyroid production.
PTU:
what does it help treat?
what does it do?
used in the treatment of hyperthyroidism.
it inhibits TPO!
What are the levels of iodine/iodide in the thyroid gland? What’s happening between the ECF and the thyroid gland?
what’s the most important aspect to remember about iodine and where it’s stored?
the iodide trap is going to take extracellular fluid iodide and shove it into the thyroid gland
there’s also an iodide leak going from thyroid gland back to the ECF
most important is to remember that iodide is going to be stored in the colloid.. it’s stored as IODINE on tyrosine of thyroglobulin (iodinated tyrosine)
in case of an issue, how much iodine is stored in the thyroglobulin in the follicular colloid?
2-3 months worth
What populations tend to have an iodine deficiency?
populations away from the coast… the seaweed and fish have iodine in it
how can you assess thyroid gland activity?
what are two types of disease that increase the uptake of iodine?
main message?
radioactive iodine uptake!
you’re measuring how much 123 iodine uptake.. hyperactive thyroid gland uptakes more of the radioactively labelled iodine.
Hyperthyroidism
Extreme stimulation of the thyroid gland (grave’s disease associated thyrotoxicosis)
so hyperthyroid uptakes way more iodine.
This explains why when we have a ton of Iodine we don’t see more T3 made… rather we see the Wolff chaikoff effect.
how is most thyroid bound in circulation?
where is this synthesized?
what does it have affinity for? how does this relate to half life?
why is this good?
1) most thyroid hormone is bound by Thyroxine binding globulin (TBG) (70% of those)
synthesized by the liver!
this binding protein has a higher binding affinity for T4 than T3… helps in having a longer half life! (T4 is 6-8 days, T3 is 1 day)
it’s good to have a pool connected to the TBG.
What is TSH more sensitive to? bound hormone or free hormone
free T4 / T3
Other than TBG, what else binds T3 and T4?
Transthyretin (TTR)
Albumin
Hypothalamus secretes TRH –> Pituitary signals TSH –> Thyroid makes T3 and T4 and it sends it to circulation where it can be bound in equilibrium with bound and free T3 and T4. which is biologically active?
the free t4 and t3!
