Thyroid Hormones Flashcards
What are the thyroid hormones and what are they derived from?
Tyrosine. Each different hormone has a different number of iodines in different positions (T4, T3, rT3).
Describe thyroid hormone synthesis
Made in the epithelial cells. TSH binds to TSHR and activates GalphaS pathway. AC and cAMP phosphorylate most of the enzymes involved in this pathway. Iodine is brought into the cell from the blood and IP3 stimulates production of thyrogobulin. As thyroglobulin is released into the colloid, THOX2 (thyroid oxidase) and TPO (thyroid peroxidase), iodinate thyroglobulin. Iodinated thyroglobulin is then stored in the colloid. TSH also stimulates production of microvilli at the apical membrane allowing reuptakes of thyroglobulin. Inside the cell T3 and T4 get released from thyroglobulin and D1/D2 play a role in converting T4–>T3. However, still more T4 (inactive) is released from the cell than T3 (active).
What is goiter?
Too much TSH leading to enlargement of the thyroid gland.
What are the causes of goiter?
- iodine deficiency
- defects in thyroid biosynthesis
- TSH receptor defect
- thyroid hormone resistance
How does iodine deficiency cause goiter?
not able to make T3 or T4 which means no negative feedback to inhibit TSH, so constant stimulation of TSHR leading to hypertrophy of the thyroid
What does thyroid hormone receptor defect lead to?
Goiter. Causes there to be increased TSH and T3/T4 in the blood. Since T3 and T4 aren’t affecting their target organs, there is increased levels in the blood. But there are also increased TSH levels because the body is trying to get those effects to happen at the tissue and it isn’t working, so it keeps secreting more TSH. It presents as hypothyroidism since no thyroid hormone effects are working, but there is both TSH and thyroid hormone present in the blood.
How are thyroid hormones carried in the blood?
by TBG (thyroxine-binding globulin), TTR (transthyretin) and albumin
Which binding protein is specific and nonspecific?
Specific=TBG, higher affinity for T4
Nonspecific= TTR and albumin, higher affinity for T4
What is the half life of T3 and T4?
thyroid hormone is mostly bound (1% unbound). T4 is more stable than T3 since the binding proteins have a higher affinity for T4 and therefore T4 has a much longer half life.
What does DI and DII do?
Are iodothyronine deiodinases that eliminate the 5’ iodine converting T4 to T3.
What does DIII do?
Eliminates the 5’ iodine on the N side to convert T4 to rT3 (inactive)
Which thyroid hormones are active and which are inactive?
T4, rT3, T2 are all inactive
T3 is active
Where is D1 located at the peripheral tissues?
D1 is on the plasma membrane where it is able to bind T4 and convert it to T3 and release T3 back out into the circulation.
Where is D2 located at the peripheral tissues?
D2 is near the nucleus and golgi. T4 enters the cell and is converted to T3 but this T3 can enter the plasma or stay in the cell and plays an important role in negative feedback in the anterior pituitary and hypothalamus. In the anterior pituitary there is only D2 so the T4 that comes in and is converted to T3 stays in the cell allowing anterior pituitary to sense how much thyroid hormone is in the blood and regulate TSH levels.
Where is D3 located at the peripheral tissues?
D3 is also located at the plasma membrane but converts T4 to rT3, inactivating it and making a hormone that cannot bind to the D receptors. Main inactivator receptor.
What are the main products of D1, D2 and D3?
D1=T3, rT3 and T2
D2=T3
D3=rT3 and T2