Thyroid Gland and Iodothyronines 6 Flashcards
Describe the anatomy of the thyroid gland?
- located at the top of the trachea
- It is bilobed and the isthmus holds the two lobes together
- They pyramid sits on top of the isthmus and is present in some people (can get a tumor here)
Describe follicles and structure
Thyroid is full of follicles comprising of follicular cells (which line the follicle), colloid (proteinaceous substance found in the follicle) and the parafollicular cells (found between the follicles which also provide hormones)
Describe the thyroid stimulus
TSH, secreted from the anterior pituitary, binds to TSH receptors that are found on the basal/serosal membrane.
What are the 5 factors TSH stimulates?
1) Iodide Uptake
2) Thyroglobulin
3) Thryoid Peroxidase (MIT/DIT)
4) Thyroid Peroxidase (coupling)
5) Endocytosis
Describe Iodide uptake in the Thyroid
- Iodide is needed for the synthesis of iodothyronines
- Iodide is pumped into the cell from the blood through IODIDE PUMPS (NIS pump as sodium/iodide symporter)
- Iodide is then pumped out of the cells and into the colloid on the apical membrane by PENDRIN PUMPS.
- TSH binding to receptor stimulates the iodide pumps
How does TSH action affect Thyroglobulin?
TSH affects the nucleus of the cells and causes Thryoglobulin (TG) synthesis. This then moves to the colloid and remains associated with the apical membrane.
Explain TPO action
TSH stimulates Thyroid Peroxidase (TPO). This, in the presence of hydrogen peroxide, oxidises Iodide to a short lived reactive iodine form in the colloid. This iodises one of the tyrosine residues on the long chained Thyroglobulin molecule. The tyrosines can be iodised on one or two positions to form either MONOIODOTYROSINE (MIT) or DIIODOTYROSINE (DIT)
Explain further TPO Action
Furter stimulation of TPO causes coupling reactions of the MIT and DIT. This cause Triiodothryonines (T3) and Tetraiodothyronines (T4) to be formed. Therefore, the colloid becones a massive store of iodothyronines
Describe TSH and Endocyotosis
TSH stimulates lysosymes to move to the apical surfaces and then the uptake of colloid into vesicle (endocytosis). The vesicle fuses with the lysosyme so enzymes can break down the proteins and liberate T3 and T4 so they can move freely into the blood stream
What are the methods of iodothyronine transport?
- Bound to Thyroxine-Binding Protein (TBG) (T3/T4 = 70-80%)
- Bound to Albumin (10-15%)
- Bound to Prealbumin (also known as tranthyretin). This binds a fair amount of T4 but not T3
- Bioactive; T3 = 0.5%, T4 = 0.05%
What are their latent half lives?
T3= 12 hours T4 = 72 hours
What are their biological half lives?
T3 = 2 days T4 = 7-9 days
Explain Deiodination
T4 is the main product of the thyroid gland but T3 is more biologically active than T4 (T3 stimulates enzyme action in the mitochondria).Therefore, in target tissues using deiodinase enzymes, T4 is converted to T3.
How is reverse T3 formed and when?
This is when T4 is deiodinated in a different position so rT3 is formed. this is biologically inactive and therefore is created in situations where a reduced metabolism is required.
Main actions of Iodothyronines
1) Increase basal metabolic rate - in every tissue other than the brain. This is important in calorigenesis and thermal regulation
2) Incrase protein, carbohydrate and fat metabolism - does this in both directions (anabolic and catabolic). This is important for normal growth.