The Thyroid Gland

Question 1

How much does the thyroid gland weigh?

Answer 1

• 15-20g

Question 2

Which thyroid hormones does the thyroid gland synthesise that are physiologically active

Answer 2

• Triiodothyronine (T₃)
• Thyroxine (T₄)

Question 3

Which 2 cell types are found in the thyroid gland

Answer 3

• C (clear) cells
• Follicular cells

Question 4

State the funcitons of the 2 cell types found in the thyroid gland

Answer 4

• C (clear) cells: Secretes calcitonin (Ca²⁺ regulating hormone)
• Follicular cells: Support thyroid hormone synthesis and surround hollow follicles

Question 5

What are thyroid follicles?

Answer 5

• Spherical structures whose walls are made of follicular cells
• Centre of the follicle is filled with colloid which is a sticky glycoprotein matrix which contains 2-3 months supply of thyroid hormone

Question 6

How to follicular cells support thyroid hormone synthesis?

Answer 6

Follicular cells manufacture enzymes that make thyroid hormones

(note: also makes thyroglobulin)

Question 7

Apart from enzymes, what else do follicular cells manufacture?

Answer 7

Thyroglobulin: A large protein rich in tyrosine residues

Question 8

After follicular cells manufacture enzymes and thyroglobulin, what happens to these products?

Answer 8

• The enzymes and thyroglobulin are packages into vesicles and exported from the follicular cell into the colloid

Question 9

What substance do the follicular cells actively concentrate from the plasma into the colloid and what does this allow?

Answer 9

• Iodine

This allows the iodine to combine with tyrosine residues to form the thyroid hormones

Question 10

How does Iodine enter follicular cells?

Answer 10

Iodine enters follicular cells from the plasma via a Na+/I-transporter (symporter)

Question 11

How does Iodine enter the colloid?

Answer 11

• Pendrin transporter

Question 12

After iodine reaches the colloid, what processes occur to form thyroid hormones?

Answer 12

• Enzymes and thyroglobulin are exocytosed into the colloid
• The enzyme thyroid peroxidase (aka thyroperoxidase) converts I^- to I₂ by removing an electron
• This catalyses the addition of iodine to tyrosine residues on the thyroglobulin molecule forming thyroid hormones

Question 13

How is triiodothyronine (T₃) formed?

Answer 13

• One iodine + tyrosine ➔ MIT
• Addition of a 2nd iodine ➔ DIT

MIT + DIT ➔ T₃

Question 14

How is thyroxine (T₄) formed?

Answer 14

• One iodine + tyrosine ➔ MIT
• Addition of a 2nd iodine ➔ DIT

DIT + DIT ➔ T₄

Question 15

After thyroid hormone synthesis in the colloid, what happens next?

Answer 15

• In response to TSH, the thyroglobulin T₃/T₄ complex is taken back into the follicular cells by endocytosis
• Within the cells, they form vesicles which contain proteolytic enzymes that cut the thyroglobulin to release thyroid hormones (T₃/T₄)

Question 16

Both T₃ and T₄ are water/lipid soluble

Answer 16

- Lipid soluble

Question 17

Both T₃ and T₄ circulate/do not circulate in the plasma

Answer 17

• Circulate

Question 18

Most T₃/T₄ circulates freely in the plasma.

True/false

Answer 18

False

More than 99.8% of T₃ and T₄ circulates in plasma bound to plasma protein.

(REMEMBER: Thyroid hormones are hydrophobic and so bind to plasma proteins due to their low solubility in water)

Question 19

Why does T₄ have a longer half life than T₃?

Answer 19

• Thyroxine Binding Globulin (TBG) has a particularly higher affinity for T₄ releasing it only slowly into the plasma

(also in the lecture: most TH circulates in the form of protein bound T₄)

Question 20

How can T₄ be converted into T₃?

And what is this process called?

Answer 20

• Remove an iodine
• Deiodinease enzymes (half deiodinated in plasma, half in target cells)

Question 21

“However 90% of TH binding to TH receptors inside cells is T3.”

(DON’T GET IT!!)

Question 22

Descibe the regulation of thyroid hormone release

Answer 22

• A stimulus (i.e cold, exercise, pregnancy) causes the trophic hormone Thyrotropin Releasing Hormone (TRH) in the hypothalamus to act on the anterior pituitary to release Thyroid Stimulating Hormone (TSH)
• TSH from the anterior pituitary in turn acts on the thyroid gland to promote hormone synthesis (T₃/T₄)
• The thyroid hormones normally act as a negative feedback signal to prevent oversecretion

Question 23

Describe how thyroid hormones function affect thier target cells

Answer 23

• Thyroid hormone (TH) binds to nuclear receptors in target cells
• The complex then binds to specefic sequences of DNA
• This changes transcription and translation to alter protein synthesis

Question 24

State some functions of thyroid hormones

Answer 24

• Increase metabolic rate (by stimulating the use of cellular O₂ to produce ATP)
• Promotes thermogenesis (production of heat)
• Increases hepatic gluconeogenesis although has no effect on BG (providing the pancreas is releasing adequete insulin)
• Net increase in proteolysis
• Net increase in lipolysis
• Critical for growth (lack of TH results in retarded growth)
• Astimulates GH receptor expression
• Essential for brain development in utero (maternal iodine deficiency = congenital hypothyroidism/cretinism)