Thyroid Gland and Iodothyronines 6

Question 1

Describe the anatomy of the thyroid gland?

Answer 1

• 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)

Question 2

Describe follicles and structure

Answer 2

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)

Question 3

Describe the thyroid stimulus

Answer 3

TSH, secreted from the anterior pituitary, binds to TSH receptors that are found on the basal/serosal membrane.

Question 4

What are the 5 factors TSH stimulates?

Answer 4

1) Iodide Uptake
2) Thyroglobulin
3) Thryoid Peroxidase (MIT/DIT)
4) Thyroid Peroxidase (coupling)
5) Endocytosis

Question 5

Describe Iodide uptake in the Thyroid

Answer 5

• 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

Question 6

How does TSH action affect Thyroglobulin?

Answer 6

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.

Question 7

Explain TPO action

Answer 7

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)

Question 8

Explain further TPO Action

Answer 8

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

Question 9

Describe TSH and Endocyotosis

Answer 9

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

Question 10

What are the methods of iodothyronine transport?

Answer 10

• 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%

Question 11

What are their latent half lives?

Answer 11

T3= 12 hours 
T4 = 72 hours

Question 12

What are their biological half lives?

Answer 12

T3 = 2 days
T4 = 7-9 days

Question 13

Explain Deiodination

Answer 13

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.

Question 14

How is reverse T3 formed and when?

Answer 14

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.

Question 15

Main actions of Iodothyronines

Answer 15

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.

Question 16

Describe Cretinism formation

Answer 16

A lack of foetal iodothryonines can cause growth delays and cretinism if not treated in the first few months. A heel-prick test measures TH and TSH

Question 17

Secondary Actions of Iodothyronines

Answer 17

• Enhance the effect of catecholamines (leads to tachycardia, glycogenolysis and lipolysis if overactive thyroid)
• Interact with other endocrine systems
• Have effects on the CNS (in brain development)
• Increased Vitamin C synthesis from retinal….

Question 18

Iodothyronines action

Answer 18

They interact with intracellular receptors and this receptor-hormone complex affects the nucleus for transcription rates. This also affects membrane transport pumps in the brain. Iodothyronines have a GENOMIC action

Question 19

Describe TSH formation

Answer 19

Neurones containing Thyrotropin Releasing Hormone (TRH) release this into the primary capillary plexus. TRH stimulates the thyrotrophs to produce TSH.

Question 20

Factors that increase Iodothyronine production?

Answer 20

• TRH

- oestrogens

Question 21

Factors that decrease Iodothyronine production?

Answer 21

• T3/T4 (directly on adenohypophysis/indirectly on hypothalamus)
• Somatostatin
• Glucocorticoids
• Ingestion of large amounts of inorganice Iodide (Wolff-chaikov effect)
• Iodothryonines (auto-negative feedback loop)

Question 22

What does high TSH indicate?

Answer 22

Problems producing T3 and T4.

Question 23

What is thryostimulin?

Answer 23

• recently discovered two uni glycoprotein found in the adenohypophysis
• Binds to thyrotrophin receptor
• Its functions are unknown.