Thyroid Hormones

Question 1

Which hormones do we mean when we say “thyroid hormones”?

Answer 1

T4 (thyroxine/tetraiodothyronine), T3 (tri-iodothyronine), calcitonin

Question 2

What does the ‘T’ in T4 and T3 mean? How about the number?

Answer 2

T= Compound based around tyrosine
Number= number of iodines attached

Question 3

How and where are thyroid hormones produced?

Answer 3

. Tyrosine iodinated on thyroglobulin (large glycoprotein with many tyrosine molecules), catalysed by thyroid peroxidase (TPO)
. In cuboidal follicular cells (in thyroid gland)

Question 4

What type of cells are found in the thyroid gland? Describe the structure of the thyroid gland.

Answer 4

. Cuboidal follicular cells (with microvilli) surround colloid (apical membrane of follicular cells facing in to colloid, basal membrane facing out)
. These are surrounded by capillaries and parafollicular C-cells

Question 5

How is T3 made?

Answer 5

. Tyrosine + iodine –> MIT (tyrosine iodinated at 3’ of ring)
. MIT + DIT –> T3 (triiodothyronine)

Question 6

How is T4 made?

Answer 6

. Tyrosine + iodine –> DIT (tyrosine iodinated at 3’ and 5’ of ring)
. DIT + DIT –> T4 (tetraiodothyronine/thyroxine)

Question 7

What are MIT and DIT?

Answer 7

Mono-iodotyrosine and di-iodotyrosine

Question 8

How is rT3 (reverse T3) made?

Answer 8

. Tyrosine + iodine –> MIT or DIT

. DIT + MIT –> rT3

Question 9

How is the production of T3 and rT3 different?

Answer 9

MIT + DIT –> T3

DIT + MIT –> rT3

Question 10

What does rT3 do?

Answer 10

Acts as an antagonist against T3

Binds to T3 receptor but doesn’t activate it, just prevents T3 from binding

Question 11

Which side of the follicular cell faces the colloid?

Answer 11

Apical/luminal membrane

Question 12

How is iodine obtained by the body to make MIT and DIT?

Answer 12

Most iodine comes from diet as iodide, then enters bloodstream and transported across follicular cells and oxidised to iodine to be added to tyrosine

Question 13

How is iodide uptaken from the blood and transported into the colloid?

Answer 13

. Sodium-iodide symporter transports iodide from blood across basal membrane into follicular cell
. Travels through cell then released out other side of cell through apical membrane via pendrin (transporter)
. Thyroid peroxidase (TPO, protein in cell membrane)oxidises iodide to iodine
. Iodine added to tyrosine to make thyroid hormones

Question 14

What is thyroid peroxidase, what does it do, and where is it found?

Answer 14

. Membrane protein
. Catalyses oxidation of iodide to iodine, iodination of tyrosine (on thyroglobulin), coupling of iodotyrosines (MIT/DIT)
. Found in apical/luminal membrane of follicular cells

Question 15

How is thyroglobulin transported from the follicular cells to the colloid?

Answer 15

Exocytosis

Question 16

What is the colloid?

Answer 16

The follicule lumen

Question 17

Where is iodinated thyroglobulin stored? How is it uptaken back into the follicular cell?

Answer 17

Stored in the colloid

Uptaken into follicular cell by endocytosis when needed

Question 18

Describe how thyroid hormones are released into the bloodstream from being stored in the colloid

Answer 18

. Thyroid hormones bound to thyroglobulin (Tg) in colloid
. Apical membrane pinches some colloid and takes some iodinated Tg into follicular cell in endosome by endocytosis
. In cytoplasm, lysosomal proteases degrade endosomes to release T3 and T4
. T3 and T4 released into bloodstream

Question 19

Where is thyrotropin-releasing hormone (TRH) secreted from?

Answer 19

Hypothalamus

Question 20

Where is thyroid-stimulating hormone (TSH/thyrotropin) secreted from?

Answer 20

Anterior pituitary gland

Question 21

Starting from the hypothalamus, describe the pathway by which secretion of thyroid hormones T3 and T4 are regulated

Answer 21

Hypothalamus releases thyrotropin-releasing hormone (TRH)
Stimulates anterior pituitary to release thyroid-stimulating hormone (TSH)
TSH stimulates synthesis and release of T3/T4 from thyroid gland

Question 22

What does TSH do?

Answer 22

. Stimulates synthesis and release of T3/T4 from thyroid gland
. Maintains integrity of thyroid gland (trophic hormone)

Question 23

What does excess TSH result in?

Answer 23

Increase in size and number of thyroid follicular cells in thyroid gland, resulting in excess production of T3/T4

Question 24

Describe how cold exposure to new-borns can cause an increase in thyroid hormones. Why is this beneficial?

Answer 24

. Neonate warm inside mother then when born exposed to cold of outside world
. Increased TRH –> increased TSH –> increase T3/T4
. Increased metabolism generates heat energy

Question 25

Describe how stress (e.g. trauma) can cause a decrease in thyroid hormones. Why is this beneficial?

Answer 25

. Stress = decrease TRH, increase somatostatin . Causes decreased release of TSH --> decreased T3/T4 . Decreased metabolism to reduce heat loss, so can harness energy to deal with stressor

Question 26

How are thyroid hormones transported in the blood? Are they active in the blood?

Answer 26

By carrier plasma proteins because they're lipophilic | No, protein-bound hormones are biologically inert

Question 27

Which measurement correlates more closely to thyroid function: free T4 or total T4?

Answer 27

Free T4

Question 28

Which group of enzymes is responsible for converting T4 to T3/rT3?

Answer 28

Deiodinase enzymes

Question 29

Describe the relative amounts of T3 and T4 produced by the thyroid gland

Answer 29

Produces mostly T4, but in target tissues most T4 is converted to mostly T3 and some rT3 (which is more biologically active)

Question 30

Which is more potent, T3 or T4? What is the effect of this?

Answer 30

. T3 more potent than T4, so most activity in target cells is mediated by T3 . T3 is the main active hormone, T4 is mainly prohormone (converted to mostly T3 and some rT3)

Question 31

What do thyroid hormones do?

Answer 31

. Increase metabolism . Stimulate growth and development . Synergistic actions with sympathetic NS/catecholamines (by upregulating expression of B-adrenoceptors)

Question 32

How is a cellular response generated when thyroid hormones bind to intracellular receptors?

Answer 32

Intracellular receptors act as hormone-regulated | transcription factors --> Alter production of proteins + biological effects

Question 33

What effect would an decrease in T3 and a increase in rT3 have?

Answer 33

Lower metabolic rate (rT3 inhibits effect of T3 by blocking T3 receptors, and low T3 plus antagonistic effect of increased rT3= slower metabolic rate)

Question 34

What would happen to the production of T3 and rT3 if the body wanted to conserve energy or in the case of disease etc.?

Answer 34

More rT3 produced than T3 (lowers metabolic rate because of rT3's antagonist effect on T3)

Question 35

Which kind of system regulates thyroid hormone secretion?

Answer 35

Negative feedback system between hypothalamic TRH, anterior pituitary TSH, and thyroid T3/T4

Question 36

What does calcitonin do? How does it do this? Which cells produce calcitonin?

Answer 36

. Decreases blood calcium levels (opposes parathyroid hormone, PTH) . Inhibits action of osteoclasts (usually break down bone) and decreases renal reabsorption of calcium . C-cells (parafollicular cells)

Question 37

How many parathyroid glands do people normally have? What do they do and how do they do this?

Answer 37

4 | Secrete PTH to increase blood calcium and phosphate levels