5 - Thyroid Hormones Flashcards
(46 cards)
What is the functional unit of the thyroid gland?
Follicles
- Follicular cells are arranged around a central cavity (lumen)
- This lumen contains colloid, which is a protein-rich fluid
What are parafollicular cells?
The cells that surround the follicles
- These cells produce calcitonin
What is the main source of iodine?
The diet
How is iodine accumulated by the thyroid follicular cells?
***Objective
- Iodide is concentrated by follicular cells in an energy-dependent manner.
- The energy of the sodium electrochemical gradient across the cell membrane powers uptake of iodide.
- The iodide ions exit the follicular cell and enter the lumen of the follicle via an iodide channel located in the apical membrane.
- This is a passive process, with iodide ions flowing down their concentration gradient.
What is thyroglobulin?
- Thyroid hormones are derived from thyroglobulin, a large, homodimeric glycoprotein
- Thyroglobulin is made by the follicular cells and secreted through the apical membrane into the lumen of the follicles, where it forms the major component of colloid
What is meant by organification of iodine?
Incorporation of iodine into thyroglobulin is referred to as the organification of iodine
Why is iodine needed?
Iodinated thyroglobulin molecules are coupled together to form T3 and T4 - thyroid hormones
What enzyme is responsible for the organification of iodine?
Thyroid peroxidase
Thyroid peroxidase is a
What does this enzyme (thyroid peroxidase) require for activity?
*** Objective
- Iodide ions (a reducing agent aka electron donor)
- Hydrogen peroxide
Iodide ions reduce hydrogen peroxide to water
The hydrogen peroxide comes from calcium-dependent NADPH oxidases, which are located near thyroid peroxidase
What happens to the oxidized iodine?
I- is oxidized to I (atomic iodine)
- Iodine reacts with tyrosine residues found within a thyroglobulin molecule
What forms from iodine and tyrosine found within thyroglobulin?
Monoiodothyronine (MIT)
What does MIT react with?
MIT can react with another iodine to form diiodothyronine (DIT)
In terms of thyroid hormone synthesis, what is meant by ‘coupling’?
*** Objective
Thyroid peroxidase enzyme functions to couple MIT with DIT or couple DIT with another DIT
These form T3 (MIT/DIT) or T4 (DIT/DIT)
Does the thyroid gland have the capacity to store hormone?
*** Objective
Yes
How does the thyroid gland store hormone?
*** Objective
There is a lot of iodinated thyroglobulin in colloid, meaning that the thyroid can just keep it there and store it
There is a 2 – 3 months supply of thyroid hormone in a normal, healthy individual
What does the release of T3 and T4 require?
*** Objective
Proteolysis of thyroglobulin
Describe the process of T3 and T4 release
*** Objective
- Thyroglobulin (big molecule which tyrosin is on) is taken back up into the follicular cells by an endocytic process
- The endocytic vesicles take the thyroglobulin to the lysosome
- A process of proteolysis releases T3, T4, MIT, DIT, peptides and free amino acids
- T3 and T4 are then trafficked out of the cell
- MIT and DIT are de-ioninated in order to conserve iodine for re-use
Which is more abundant, T3 or T4?
*** Objective
T4
More T4 is formed than T3
Typical ratio is 5-7 T4 for every T3
Which is the more biologically active hormone, T3 or T4?
*** Objective
T3
Both T3 and T4 are biologically active in their “free” form, but more T3 is free than T4, so it is considered to be more biologically active
Where does the conversion of T4 to T3 occur?
*** Objective
About 40% of T4 is converted to T3, particularly in the liver and kidneys
How does the conversion of T4 to T3 occur?
*** Objective
Deiodination
There are three classes of deiodinated enzymes (deiodinases)
What process accounts for thyroglobulin found in the serum?
*** Objective
Transcytosis
Certain endocytic vesicles are routed from the apical membrane to the basolateral membrane, where they thyroglobulin that they contain is released into the bloodstream by exocytosis
What is the clinical significance of thyroglobulin in the serum via transcytosis?
*** Objective
Can be a sign of…
- Thyroiditis
- Graves disease
- Thyroid malignancy
Describe how thyrotropin releasing hormone (TRH) signals thyroid stimulating hormone (TSH; thyrotropin) release.
*** Objective
- Parvicellular neurons of the hypothalamus release TRH
- TRH goes to the anterior pituitary via the portal hypophysial system
- TRH binds to a G-protein receptor
- Phospholipase C is activated
- Calcium is released, which triggers exocytosis of vesicles containing TSH (thyroid stimulating hormone; thyrotropin)