Case 9- thyroid hormones

Question 1

Hypothalamus- pituitary-thyroid (PHT) axis

Answer 1

In response to a stimulus, the hypothalamus releases thyrotropin-releasing hormone (TRH) which acts on the anterior pituitary. The anterior pituitary releases the thyroid stimulating hormone (TSH) into the blood. TSH then travels to the thyroid gland and stimulates production of thyroid hormones (T3 and T4)

Question 2

Effects of TSH

Answer 2

↑ in size of follicular cells
↑ lysosomal activity
↑ pinocytosis of colloid
↑ iodination
↑ iodine uptake
↑ thyroglobulin synthesis

Question 3

Thyroid hormone feedback

Answer 3

A type of negative feedback. An increase in T3 and T4 in the blood causes a reduction in TRH and TSH release

Question 4

Hormones released- Hypothyroidism

Answer 4

↓ T3 & T4 but ↑ TSH

Question 5

Hormones released- Hyperthyroidism

Answer 5

↑ T3 & T4 but ↓ TSH

Question 6

Local control of Thyroid hormones

Answer 6

There is more T4 in the body but T3 is more active. Most plasma T3 is derived from the peripheral metabolism of T4. Conversion from T4 to T3 requires the removal of an iodine by a deiodinase enzyme. Thus, most T3 in the tissues is a result of tissue-specific type 2 deiodinase activity on T4. T4 can also be metabolised to reverse T3 which is inactive. By controlling the balance of T3 and rT3 tissues can manage their local thyroid status.

Question 7

Receptor affinity for T3 and T4

Answer 7

All receptor types except TRa2 have a higher affinity for T3 than T4

Question 8

Mechanism of action of T3 and T4

Answer 8

Circulating T3 and T4 require carrier mediated transport to cross the cell membrane. The 5’ deiodinase enzyme converts T4 to T3 in the cytoplasm. There are four thyroid hormone receptors-TR α1, α2, β1 and β2 (TRα2 does not bind T3). They exist as homodimers TR-TR or as heterodimers TR-RXR (retinol X receptor) bound to the thyroid response element (TRE) on the DNA. When T3 binds to the thyroid hormone receptor, gene transcription is activated to form mRNA followed by translation to a protein.

Question 9

Proteins produced by T3

Answer 9

They are functional, involved in metabolism and structural, involved in growth

Question 10

Metabolic function of the thyroid gland

Answer 10

1) Increase basic metabolic rate
2) Increases Glycolysis
3) Increases O2 consumption
4) Increases Thermogenesis
5) Increases protein turnover

Question 11

Growth and development function of the thyroid gland

Answer 11

1) Fetal neural development

2) After birth it helps bone growth and tooth development

Question 12

Neurological functions of the thyroid gland

Answer 12

1) Maintains emotional tone

2) Increases alertness, memory, reflexes and wakefulness

Question 13

Cardiovascular function of the thyroid gland

Answer 13

1) Increase in cardiac output (HR and SV)
2) Increase in systolic pressure
3) Enhances catecholamine action via an increase in beta-adrenergic receptor activation

Question 14

Reproductive function of the thyroid gland

Answer 14

1) Permissive role in males and female

Question 15

Thyroxine (T4)

Answer 15

The most abundant hormone produced

Question 16

Triiodothyronine (T3)

Answer 16

The most active thyroid hormone

Question 17

Caticonin

Answer 17

Involved with calcium homeostasis in the blood in conjugation with the parathyroid gland

Question 18

T3 and T4 synthesis- entering the cell

Answer 18

• TSH stimulates follicular cells to produce and excrete the protein Thyroglobulin into the colloid of the thyroid gland. Thyroglobulin contains Tyrosine
• Iodide is transported from the blood into the follicular cell through the sodium/iodide cotransporter.
• The iodide then moves into the colloid through the pendrin transporter.

Question 19

T3 and T4 synthesis- Thyroid peroxidase

Answer 19

• Thyroid peroxidase is expressed on the apical membrane of follicular cells and oxidises iodide (negative) to Iodine.
• Thyroid peroxidase iodises thyroglobulin by attaching iodine tyrosine residues, when one is attached it creates MIT, when two are attached it creates DIT.
• Thyroid peroxidase also contributes to the coupling of the Tyrosine residues on Thyroglobulin. When DIT and MIT residues come together you get T3, when DIT and DIT residues come together you get T4.

Question 20

T3 and T4 synthesis- follicular cell

Answer 20

• Thyroglobulin (containing the tyrosine residues) then enters the follicular cell and lysosomes fuse with the vesicle (containing Thyroglobulin) inside the cell releasing the enzymes. This then cleaves the Thyroglobulin into T3 and T4.
• There is then exocytosis of the thyroid hormones into capillaries where it binds with its transport proteins and moves around the body.

Question 21

Free and bound thyroid hormones

Answer 21

The free hormone is active and the bound hormone acts as a reservoir. The increase or decrease in binding protein concentration changes the proportion of thyroid hormone that is free and biologically active. These proteins are produced by the liver and this process is stimulated by oestrogen and can therefore be affected by pregnancy and HRT.

Question 22

What are thyroid hormones bound to?

Answer 22

0.1% of the thyroid hormones are free in the blood (unbound). The rest are bound to thyroid transport proteins: thyroid binding globulin (TBG) (70%), Albumin (20%) and transthyretin.