Endocrine Physiology: Thyroid Hormones

Question 1

*List the steps in the biosynthesis. storage, and secretion of triiordothyronine (T3) and Thyroxine (T4)

Answer 1

A

Question 2

*Describe the factors that control the synthesis, storage and release of thyroid hormones

Answer 2

A

Question 3

*Explain the importance of thyroxine binding protein on free and total thyroid hormones

Answer 3

A

Question 4

*Explain the significance of the conversion of T4 to T3 and reverse T3 (rT3) in extra-thyroidal tissues

Answer 4

A

Question 5

*Describe the actions of thyroid hormones of development and metabolism

Answer 5

A

Question 6

*Describe the causes and consequences of a) oversecretion and b) undersecretion of thyroid hormones. Explain why either conditions can cause an enlargement of the thyroid gland.

Answer 6

A

Question 7

What structure produces thyroid hormone and cortisol?

Answer 7

Thyroid hormone and cortisol are produced by HYPOTHALAMIC AXIS

Question 8

*What are the characteristics for amine hormones? Do Thyroid hormones (T3, T4) behave like other amine?

Answer 8

Amine hormones: catecholamines
1. rapid (enzymatic) synthesis
2. Stored in secretory granule
3. Water soluble
4. Short-half life
5. membrane receptor
NO, thyroid hormones DO NOT behave like other amine hormones.
Thyroid hormones:
1. Do NOT have rapid (enzymatic) synthesis
2. They are NOT stored in secretory granules. thyroid hormones are stored outside cells
3. They are NOT water soluble. Thyroid hormones need Binding proteins
4. They do NOT have short-life. T4 has short-life of 7 days; T3 has short-life of 1 day (long compared to catecholamines, have half life of 2-3 mins)
5. They are NOT membrane receptors. Thyroid hormones (t3, t4) have receptors in Nucleus.

Question 9

Describe the structure of the thyroid gland. What happens when you repeatedly stimulate the thyroid? What are the causes of goiter?

Answer 9

Thyroid gland- bow tie shape that has 2 lobes
The SIZE of thyroid INCREASES when you repeatedly stimulate thyroid.
Goiter caused by Iodine Insufficiency or inflammation of thyroid gland (repeatedly stimulate thyroid),

Question 10

What is thyroid hyperplasia?

Answer 10

Thyroid Hyperplasia- enlargement of thyroid glands due to abnormal proliferation of thyroid epithelial cells (increase in number of cells).

Question 11

What is a colloid? What surrounds the colloid? What happens when colloid is in Basal vs stimulated state?

Answer 11

Colloid - place for storing thyroid hormones.
Follicular cells surround the colloid and organize themselves into a sphere in basal (resting state)
Colloid is stimulated by TSH, and follicular cells become COLUMNAR, causing hyperplasia (increase cell number).

Question 12

*What are the three major steps for thyroid hormone synthesis?

Answer 12

3 steps for thyroid hormone synthesis:

1. Uptake and concentration of Iodide (I-) in the gland
2. Oxidation and incorporation of I- (Iodide) into tyrosine’s phenol ring.
3. Coupling of two iodinated tyrosines to form T4(4 iodides), or T3 (3 iodides)

Question 13

Why is iodine important? Where can it be obtained? What is the minimum requirement of Iodide? How does it compare to avg U.S intake?

Answer 13

Iodine- a critical micronutrient
-few food sources are rich in iodide
-Seaweed (kombu kelp, wakame, nori), Iodized table salt.
Minimum daily requirement of Iodide: 80 ug.
Us average daily intake: 300-400 ug
stored Iodine within thyroid gland is 100 x greater than daily need
-protected for 2 months from iodine deficiency.

Question 14

Describe how levels of iodine affects thyroid synthesis. What is Wolff-Chaikoff effect?

Answer 14

LOW levels of iodine intake DECREASES Rate of thyroid synthesis
HIGH levels of iodine intake (> 2 mg/day) suppresses thyroid synthesis: Wolf-chaikoff effect
Wolf-Chaikoff Effect: autoregulatory process that occurs when one takes in too much iodine.
If you ingest too much iodine, it cause SHUT DOWN of thyroid hormone synthesis (for 10 days), and you will not have any iodine.

Question 15

*Further elaborate on Iodide uptake.

Answer 15

Iodine is actively transported into the thyroid gland against an electrochemical gradient by 2 Na+ 1 I- symporter (NIS)
When iodide is transferred from blood to follicular cells, Na+ goes down concentration gradient and Iodine goes UP its concentration gradient.
Na+ K+ ATPase allows Na+ go down its [ ] gradient

Question 16

*Where is Na+I symporter located? Where is Pendrin I- Symporter located?

Answer 16

Na+ I symporter located in Basement membrane
helps iodide get transported into gland and then moved across cells from basolateral side (vascular) to apical (follicular) side.
Pendrin I- an Iodide-chloride transporter (Na+ independent) that transports iodide into lumen.

Question 17

What molecules block active transport of I- (Iodine)? What molecules block iodination of thyroglobulin?

Answer 17

CLO4- and SCN- block active transport of I-.

Antithyroid drugs block iodination of thyroglobulin.

Question 18

What is organification?

Answer 18

Organification: synthesis of T3 and T4 and storage of the hormones in thyroglobulin

Question 19

*Further elaborate on Tyrosine iodination.

Answer 19

Tyrosine Iodination:
The Glycoprotein thyrogloublin- scaffold structure with lots of tyrosine
- I is oxidized and incorporated into tyrosine both by enzyme Thyroid PEROXIDASE (TPO).

Question 20

*Elaborate on Coupling of iodinated molecules with thyroglobulin (by TPO)

Answer 20

Coupling of Iodinated molecules with Thyroglobulin (By TPO):
After thyroglobulin is made, and MIT (monoiodotryrosine) and DIT (Diiodotyrosine) is made coupling with MIT and DIT by enzyme TPO occurs.
Coupling of MIT and DIT forms T3 (triiodothyroxine).
Coupling of 2 DIT’s form T4 (thyroxine)

Question 21

What is the ratio of T4 to T3 synthesized?

Answer 21

10-20:1
more T4 (10-20) for 1 T3 (1).
This occurs unless I- is limited.

Question 22

*Explain what occurs when thyroglobulin is endocytosed and hydrolyzed

Answer 22

Thyroglobulin is endocytosed and hydrolyzed:

• secretion of thyroid hormone
• Thyroglobulin enters via ENDOCYTOSIS
• Lysosomal proteases hydrolyze the thyroglobulin, and causes T3 and T4 to be released.
• MITs and DITs are then deiodinated and I- is recycled.

Question 23

*Describe the secretion of hormone from thyroid? How much of T4, T3, or rT3 is secreted? What is peripheral conversion?

Answer 23

Secretion from thyroid:
-90% T4(inactive form)
-9% T3 (4x more potent; ACTIVE hormone)
-1% rT3.
-Peripheral Conversion of T4 to T3 occurs when one Iodine molecule (on 5’ position) is removed from T4 which converts hormone into active form T3.
also, T4 converts to Reverse T3 (rT3) if Iodine removed from (5’ position).

Question 24

What kind of hormone is T4?

Answer 24

T4 is a PROHORMONE (precursor hormone for T3; active form).

Question 25

*What factors wins (hormone used) when one is starving and cold?

Answer 25

T3 WINS, when one is starving or cold.
T4 decreases and becomes T3 (active form), during Fasting, Malnutrition, physical trauma, drugs (PTU, proranolol, amiodarone), systemic illness, and Old age

Question 26

*What happens to Thyroid hormone during illness and increasing age?

Answer 26

Illness, and increasing age will make more of reverse T3.
When body is cold you make more T3.
When you are starving make more reverse T3 (rT3)
thyroid hormone increases metabolic rate which requires a lot of energy.