Function of the thyroid gland
Plays an important role in regulating metabolism & body weight
What are the products of the thyroid?
T3 - Triiodothyronine
T4 - Tetraiodothyronine (thyroxine)
Calcitonin
What is the major product of the thyroid?
T4
What is the most active product of the thyroid?
T3
What does calcitonin do?
Involved in calcium homeostasis
Structure of the thyroid gland
Biggest endocrine tissue/gland in the body
Found in the neck – below adams apple, above sternal notch & infront of the trachea
2 lobes with a connecting isthmus
Rich blood supply
2-4 pairs of parathyroids imbedded in posterior of thyroid
What are the 2 lobes of the thyroid gland connected by?
Isthmus
Why does the thyroid gland need a rich blood supply?
To carry thyroid hormones away & deliver thyroid with iodine – key ingredient to making thyroid hormones
What do parathyroids do?
Produce parathyroid hormones
Important in controlling calcium & phosphate balance
What is the functional unit of the thyroid gland?
Follicles - follicular cells
Single layer of cells surrounding a pool of colloid
What happens in the colloid?
Production & storage of thyroid hormones
Relatively large store
Grows & shrinks all the time
What are C cells?
C cells secrete calcitonin
Generally bigger than colloid
How are thyroid hormones produced?
By iodination and coupling of tyrosine
What is thyroglobulin?
Tyrosine rich
Produced by follicular cells and moved into the colloid
Glycoprotein synthesised by follicular cells and released into the follicular lumen (colloid) by exocytosis
What happens as the follicular-colloid border?
Tyrosine residues within thyroglobulin are iodinated in the presence of the enzyme thyroperoxidase
What are T1 and T2?
Precursors
T1 = monoidotyrosine
T2 = diidotyrosine
What are T3 and T4?
Active hormones
How are T3 and T4 produced?
The coupling of T1 and T2 under the control of thyroperoxidase
When is tyrosine iodinated?
When in moves into the colloid
What happens in the iodination of tyrosine?
1 iodine added = monoidotyrosine
2 iodines added = diiodotyrosoine
thyroperoxidase enzyme needed
What happens in the coupling of precursors?
Tetra T4 = composed of 2 di
Tri T3 = composed of a mono and a di
Where is thyroglobulin produced from?
Follicular cells
How is iodine transported into the follicular cells?
By sodium coupled iodine transporters
Uses the Na gradient – allows I to be taken out of the blood into the cell
What is TPO?
Thyroperoxidase
What does TPO do?
Catalyses iodination and coupling
How does thyroglobulin enter the follicular cells?
By pinocytosis/endocytosis
How happens when thyroglobulin has entered the follicular cell?
Fuses with lysosomes which contain proteases that break down thyroglobulin
When broken up it will release T1, T2, T3 & T4
What happens to T1 and T2 in the follicular cell?
T1 and T2 are not active so no point in being moved into the blood
T1 and T2 in the cells are broken down again and iodine is recycled back into the colloid
What happens to T3 and T4 in the follicular cell?
T3 & T4 are active so are moved into the blood – act as steroid hormones (lipophilic)
Have to be bound to a protein in the blood to be carried around as they are not soluble
Thyroid binding proteins - Don’t bind all of the T3 & T4
Free T3 and T4 is what binds to receptors and causes an effect
Half life of T4
Around 6 days
Half life of T3
Around 10 hours
Tissues can convert T4 to T3 when its needed –T4 acts as a reservoir
What are the 3 major thyroid transporting proteins produced by the liver?
Thyroxine-binding globulin
Thyroxine-binding prealbumin
Albumin
What does the hypothalamus do?
Decides how much releasing hormone (TRH) it releases into the anterior pituitary
How does the TRH work?
If TRH is released it will act on thyrotrophs in the anterior pituitary & stimulate them to produce TSH (thyroid stimulating hormone)
TSH travels in the blood to thyroid gland, act on walls of follicular cells to increase thyroid hormone production
Negative feedback
How does TSH effect the thyroid gland?
Increase iodine uptake Increase thyroglobulin synthesis Increase iodination of thyroglobulin Increase pinocytosis of colloid Increase lysosomal activity Increase in size of thyroid cells (cuboidal to columnar)
Metabolism of thyroid hormones
Most plasma T3 is derived from peripheral metabolism of T4 produced by the thyroid.
This can be a “step up” or “step down” process
What are the 3 enzymes involved in thyroid hormone metabolism?
1,5’-deiodinase
2,5’-deiodinase
3,5’-deiodinase
What is 1,5’-deiodinase?
Enzyme involved in metabolism of thyroid hormones
Most abundant enzyme
Provides T3 to the plasma
Step up process
What is 2,5’-deiodinase?
Enzyme involved in metabolism of thyroid hormones
Active in the brain and pituitary
Provides T3 in the CNS
Step up process
What is 3,5’-deiodinase?
Enzyme involved in metabolism of thyroid hormones
Inactivates T4 by converting it to rT3 (reverse T3) - takes iodine group off at the wrong place
Most T4 is deactivated to rT3
Step down process
Where are thyroid hormone receptors found?
In the nucleus of the cells
Receptor is bound to the DNA
When hormone isn’t bound, receptor blocks gene transcription
What are the 4 main types of thyroid hormone receptors?
Alpha 1
Alpha 2
Beta 1
Beta 2
Which thyroid hormone receptor doesn’t bind T3?
Alpha 2
Do thyroid hormone receptors have a high affinity for T3 or T4?
T3
What is hypothyroidism?
Underactive thyroid or low thyroid, is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone
Symptoms of hypothyroidism
- General tiredness and lethargy
- Bradycardia
- Mental slowness
- Cold intolerance
- Weight gain
- Depression (in about 50% of cases)
- Dry skin
- Puffy hands and face
What is hyperthyroidism?
Overactive thyroid
Occurs when your thyroid gland produces too much of the hormone thyroxine
Accelerates your bodies metabolism
Symptoms of hyperthyroidism
- Heat intolerance
- Weight loss
- Warm moist skin
- Tachycardia (atria fibrillation and heart failure)
- Fine tremor of fingers
What is Graves disease?
Common cause of thyrotoxicosis (excess of thyroid hormone in the body)
Autoimmune condition in which auto-antibodies stimulate the TSH receptor
- “Stare” - upper eyelid retraction
- “Bulging eyes” – swelling of muscles in orbit pushing eyeball out
- Goitre – enlarged thyroid due to over stimulation