The Thyroid and iodothyronines

Question 1

Describe the structure of the thyroid glands

Answer 1

Bi-lobal and located by the trachea with the pyramid isthmus running down the middle. Each follicle consists of a colloid surrounded by follicular cells, surrounded by parafollicular cells

Question 2

What are thyroid hormones known as

Answer 2

Iodothyronines

Question 3

What is the difference between T3 and T4

Answer 3

T3 is the active hormone while T4 is the main hormone product of the thyroid gland

Question 4

Describe the synthesis of iodothyronines

Answer 4

1. TSH binds to TSH receptor
2. Iodide Trapping using NIS (Na-I Symporter) – secondary active transport. Sodium conc. gradient maintained via Na+ K+ ATPase
3. Iodide pumped into colloid using Pendrin Pump (I-/Cl- antiporter)
4. Thyroglobulin synthesised and diffuses to colloid
5. I- is rapidly oxidised to I* via the enzyme thyroid peroxidase (TPO) in the presence of H2O2.
6. I* attaches to a tyrosine on a molecule of TG. Also catalysed by TPO
7. 1 I* added = 3-mono-iodotyrosine (MIT). 2 I* added = 3,5-di-iodotyrosine (DIT).
8. Coupling occurs: TPO and H2O2 combine a DIT from one TG to either an MIT or another DIT on another TG = T3/4
9. Lysozome moves towards the apical membrane and takes up T3/4 via endocytosis
10. Proteolysis cleaves T3 and T4 from the TG.
11. The T3/T4 diffuse towards the basolateral membrane

Question 5

How are iodothyronines transported

Answer 5

Bound to a protein: thyroid-binding globulin, albumin or prealbumin

Question 6

What is the proportion of proteins used for binding

Answer 6

TBG = 70-80%
Albumin = 10-15%
Prealbumin

Question 7

What happens to the other 0.05%/0.5% of T4/T3

Answer 7

Unbound and travel freely

Question 8

What is deiodination

Answer 8

Conversion of T4 into active T3

Question 9

Describe the process of diodination

Answer 9

1. T4 enters the cell
2. Conversion to T3
3. T3 binds to the TH receptor on the nucleus
4. Transcription of genes and proteins synthesis
5. T3 stimulated metabolic activity in the mitochondrion

Question 10

What are the actions of TH

Answer 10

Fetal growth and development
Untreated congenital hypothyroidism/cretinism
Increase basal metabolic rate
Protein, carb and fat metabolism
Potentiate actions of catecholamines
Effects on the GI, CNS, reproductive system

Question 11

What are the latent periods for thyroid hormones

Answer 11

T3= 12 hrs
T4= 72 hrs

Question 12

What are the half lives for thyroid hormones

Answer 12

T3 = 2 days
T4 = 7-9 days

Question 13

How is thyroid hormone release regulated

Answer 13

TRH in the hypothalamus stimulates thyrotrophs to make TSH. T4/3 suppress the production of TSH.

Question 14

How many iodide affect thyroid hormone release

Answer 14

Inhibits release of thyroid hormones (wolff-chaikoff effect)

Question 15

What other factors may affect thyroid hormone release

Answer 15

Oestrogens (+)

Glucocorticoids (-)

Question 16

What is the colloid

Answer 16

Extracellular matrix where T3 and T4 are synthesised