Throid hormone synthesis and action

Question 1

Briefly explain the embryology of the thyroid

Answer 1

• A downgrowth of pharyngeal endoderm from the pharynx

- C cells from ultimobranchial body (most caudal pharyngeal pouch)

Question 2

What is the lumen of thyroid follicular cells filled with?

Answer 2

-Protein rich colloid

Question 3

Where are the microvilli in a thyroid follicular cell?

Answer 3

On the colloidal side= you want an increased SA to help get protein and iodine into/ out of the colloid

Question 4

Where do you find C-cells?

Answer 4

• In the thyroid

- In the connective tissue near the follicles

Question 5

What does calcitonin do?

Answer 5

Lowers blood calcium

Question 6

What are thyroid hormones derived from?

Answer 6

Amino acid: Tyrosine

Question 7

What are the names of the 2 thyroid hormones?

Answer 7

T4=Thyroxine

T3= Triiodothyronine

Question 8

Discuss iodine uptake in the thyroid gland

Answer 8

• Iodide in the circulating blood moves into the thyroid gland
• Moves into the follicular cells by secondary active transport
• Na/I symport in the basal membrane (stimulated by TSH)
• Iodine in colloid is 30x more concentration that in blood

Question 9

Discuss the role of thyroglobulin in thyroid hormone synthesis

Answer 9

• Thyroglobulin is synthesised by follicular cells

- It is processed by the Golgi-Enters the follicular lumen by exocytosis

Question 10

How does iodination occur?

Answer 10

• It is catalysed by TPO
• TPO is located in the apical membrane
• Iodide is oxidised to iodine as it is transported across the colloid membrane
• Iodine is then added onto thyroglobulin by an iodinase enzyme - reaction is catalysed by TPO

Question 11

What is the coupling reaction involved with thyroid hormone synthesis?

Answer 11

Tyrosine binds with an iodinase to form monoiodotyrosine and diiodotyrosine-> other iodines are added and the end result in Thyroxine (T4)

Question 12

How is the thyroid hormone excreted?

Answer 12

• The thyroglobulin in the colloid reenters the cell via endocytosis
• Lysosymes fuse with the endocytic vesicle and pinch off T4 and T3 from the thyroglobulin
• T3 and T4 are lipid soluble so can move through the basal membrane into the capillary
• Thyroid binding globulin and albumin transport the T3 and T4 around the blood.

Question 13

Which thyroid hormone has a higher affinity?

Answer 13

T4

Question 14

What is the half life of both T3 and T4?

Answer 14

T3=6 hours
T4=12 hours
(in the dog)

Question 15

What does the phrase ‘latent period’ refer to with thyroid hormone transport?

Answer 15

• Due to the fact that the hormones are lipid soluble -they are bound in the blood.
• Due to this the changes occur more slowly as it has to first bind and then unbind before cellular uptake occurs

Question 16

Where is T4 deiodinated to triiothyronine?

Answer 16

In cells of most tissues

Question 17

What is rT3?

Answer 17

• Reverse T3
• It is an inactive form of T3- can be produced by the deiodination of T4 in the liver.
• Conversion of T4 to rT3 helps slow metabolism = CONSERVES ENERGY

Question 18

Explain the HPO axis as regards to thyroid hormones

Answer 18

• Hypothalamus secretes more TRH to increase conc of thyroid hormones-> acts on the anterior pituitary gland. Stimulates production of TSH which is released into the blood. When TSH reaches the thyroid is activates second messengers to increase thyroglobulin production and hence hormone production
• T3 and T4 = neg feedback on hypothalamus

Question 19

Which signal transduction pathway do most anterior pituitary hormones use?

Answer 19

Adenyl cyclase

Question 20

What are the 5 actions of TSH?

Answer 20

1) Increase endocytosis and proteolysis of thyroglobulin from colloid
2) Increase activity of the Na/I symport
3) Increased iodination of tyrosine
4) Increased size/ secretory activity of thyroid follicular cells
5) Increased number of follicular cells