PH1124 - thyroid hormones

Question 1

how and when does the thyroid gland develop? (3)

Answer 1

• appears very early in life

- develops about four weeks after conception as an epithelial invagination of the tongue

Question 2

what is the anatomy of the thyroid gland? (4)

Answer 2

• composed of 2 large lobes either side of the trachea below the larynx and joined by the isthmus
• there is a rich blood supply from thyroid arteries
• innervated by the autonomic nervous system
• pyramidal lobe is often present
• butterfly shape

Question 3

what is the cellular structure of

the thyroid gland? (3)

Answer 3

• its cells are arranged in follicles
• there are millions of follicles in a thyroid gland
• follicles are spherical bodies composed of epithelial cells surrounding a colloidal storage protein (thyroglobulin)

Question 4

what does the height of epithelial cells depend on in the thyroid gland? (2)

Answer 4

• inactive; epithelial cells are flattened with a large colloidal mass
• active; cells are columnar in shape with a small colloidal lumen

Question 5

what are the parafollicular C cells?

Answer 5

• large epithelial cells that lie between the follicles and produce calcitonin

Question 6

what are the main hormones produced by the thyroid gland? (2)

Answer 6

• T3

- T4

Question 7

how are thyroid hormones made?

Answer 7

• dietary iodide is taken up by an iodide pump from the blood
• at the apical surface I- is oxidised by hydrogen peroxide from thyroid peroxidase to I2
• I2 is immediately incorporated into tyrosyl residue covalently bound to thyroglobulin TG at apical border to form MIT and DIT
• MIT and DIT are coupled by thyroid peroxidase to form T3 and T4

Question 8

how are thyroid hormones secreted?

Answer 8

• TSH causes endocytosis and proteolysis by lysosomes of TG-hormone complex
• this is where thyroids hormones are stored in the colloid

Question 9

what simulates the uptake of iodide by the thyroid? (3)

Answer 9

• TSH (thyroid stimulating hormone)
• iodine deficiency
• TSH receptor antibodies

Question 10

what are the anions that inhibit the iodine pump? (4)

Answer 10

• I-
• perchlorate (ClO4-)
• thiocyanate (SCN-)
• pertechnetate (TcO4-)

Question 11

how are the thyroid hormones transported? (2)

Answer 11

• transported in the plasma bound to proteins where T3 is less avidly bound than T4
• only free hormone not bound is biologically active

Question 12

what are the proteins that thyroid hormones bind to in plasma? (3)

Answer 12

• thyroid binding globulin
• transthyretin
• albumin

Question 13

which thyroid hormone is more potent?

Answer 13

• T3 is approx 10 times more potent than T4

Question 14

how are thyroid hormones metabolised? (2)

Answer 14

• T4 is de-iodinated to T3 in the periphery (liver and kidney)
• T3 and T4 are conjugated to glucuronide or sulphate in the liver and excreted in the bile

Question 15

how is iodine excreted?

Answer 15

• excreted in the urine or re-circulated to the thyroid

Question 16

what is TRH?

Answer 16

• thyrotropin releasing hormone

Question 17

how is the release of thyroid hormones regulated?

Answer 17

• a stimulus causes the hypothalalmus to release TRH which causes the anterior pituitary to release TSH
• this causes the thyroid glad to produce T3 and T4
• this directly stops the productions of TSH from the anterior pituitary therefore its a negative feed back loop

Question 18

how do somatostatin and dopamine effect the production of T3 and T4?

Answer 18

• they cause the release of TSH from the anterior pituitary to be inhibited
• less T3 and T4 is secreted from the thyroid gland

Question 19

what is the role of TRH? (2)

Answer 19

• stimulates the release of thyrotrophin or thyroid stimulating hormone (TSH) from the anterior pituitary
• releases prolactin

Question 20

what is TSH?

Answer 20

• thyroid stimulating hormone

Question 21

what does TSH do to the thyroid?

Answer 21

• acts on specific receptors on basal membrane

- increases synthesis of iodine pumps, thyroglobin and thyroid hormones

Question 22

what is the release of TSH inhibited by? (6)

Answer 22

• thyroid hormones
• cortisol
• growth hormone
• oestrogens
• dopamine
• somatostatin

Question 23

what is the mechanism of action for thyroid hormones at the nuclear level? (5)

Answer 23

• T3 and T4 enter the cell by passive diffusion or active uptake
• T4 is then de-iodinated to T3
• T3 is actively transported into the nucleus and binds to cytosolic thyroid hormone binding protein (CTBP)
• this ensures T3 binds to thyroid receptors in the nucleus already bound to regulatory thyroid hormone response elements TREs
• thyroid hormone receptor auxiliary protein (TRAP) is then necessary to stabilise TR binding to DNA to either transcribe or inhibits genes

Question 24

what is the mechanism of action for thyroid hormones at the cellular level? (3)

Answer 24

• T3 binds to membrane-associated receptors to activate Na+/K+ ATPase pump
• this causes an increased uptake of glucose and amino acids
• T3 also directly activates mitochondria to increase energy production

Question 25

how do thyroid hormones control basal metabolic rate?

Answer 25

- via calorienesis

Question 26

what is calorigenesis?

Answer 26

- increase O2 consumption in all tissues (except brain, spleen, testes and anterior pituitary) causing increased heat production - iimportant for thermoregulation - does this by synthesizing new ATPase pumps in cell membrane but also directly activates mitochondria

Question 27

what does calorigenesis block?

Answer 27

- blockers of Na+/K+ ATPase pumps such as cardiac glycosides (dogoxin) inhibit actions of thyroid hormones

Question 28

what are the physiological actions of the thyroid hormones?

Answer 28

- calorigenesis - carbohydrate, protein and fat metabolism - maturation of central nervous system - skeletal growth and maturation