Thyroid+ Iodothyronines

Question 1

Structure of thyroid

Answer 1

Trachea behind
2 lobes of thyroid gland
Isthmus in middle, pyramid on top of isthmus
Made of follicles (spheres): colloid surrounded by follicular cells
Outside follicles, there are parafollicular cells

Question 2

Thyroid action

Answer 2

1. TSH secreted from anterior pituitary gland in blood
2. TSH binds TSHR (Thyrid Stimulating Hormone Receptor) on basolateral membrane on follicular cell
3. Stimulates uptake of iodide into follicular cells through NIS (Sodium iodide symporters) on basolateral membrane of follicular cell
4. Iodide transported into follicular cell+ into colloid through iodide transporters
5. TSHR activation also stimulates TG (Thyroglobulin) production (involves nucleus machinery)
6. TG transported into colloid
7. TG iodinated on tyrosine residues, catalysed by TPO (thyroproxidase) and H2O2
8. Product= Monoiodotyrosine or Diiodotyrosine
9. MIT+ DIT combined in coupling reaction into either T3 or T4 (name changes from tyorosine to thyronine during coupling reaction) (T4= Thyroxine)
10. TSHR also stimulates lysosomes to move towards apical membrane + thyroglobulin with iodine bound to it taken up into follicular cells through lysosomes+ released into blood

Question 3

Transport in blood

How much is unbound/ bioactive?

Answer 3

Bound to plasma proteins:
Thyroid-binding globulin (most) (Different from TG)
Albumin
Prealbumin (transthyretin)

0.05% T4, 0.5% T3

Question 4

Deiodination

Answer 4

T4 (Thyroxine)= main hormone product of thyroid

T3= bioactive form, so T4= deiodinated to T3 in target tissues or deiodinated into reverse T3= inactive

Question 5

Mechanism of thyroid hormones

Answer 5

1. T3 enters cells, T4 enters cells+ converted to T3
2. T3 binds to THR (Thyroid Hormone Receptor) in nucleus
3. Initiates transcription= increased protein synthesis
4. T3 also stimulates metabolic activity in mitochondria
5. T3 also has non-nuclear actions on ion channels

Question 6

Thyroid hormone actions
Untreated congenital hypothyroidism= ?
Testing?
Thyroid hormone actions in adults?

Answer 6

Foetal growth and development
Cretinism (iodine deficiency)
New-born’s heel-prick test tests for TH+ TSH

Increased basal metabolic rate- IMP
Protein, carbohydrate, fat metabolism= weight loss, increased appetite
Increases effect of catecholamines= increased tachycardia (palpitations)+ lipolysis
Effects on GI (diorrhea), CNS (agitation, restlessness), reproductive system (infertility, irregular periods, affects menstrual cycle even if its underactive)

Question 7

Latent period of thyroid hormones (effect after secretion)

Half-lives of thyroid hormones

Answer 7

T3= 12 hours
T4= 72 hours

T3= 2 days
T4= 7-9 days

Question 8

Control of TH production- diagram

Slide 13, lecture 6

Answer 8

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