The Thyroid Gland and the Iodothyronines (6)

Question 1

describe the structure of the thyroid gland

Answer 1

shield like shaped organ. it is made up of 4 parts - the right lobe, left lobe, isthmus which connects the two lobes and the pyramidal lobe which projects superiorly out of the isthmus. consists of the thyroid and parathyroid glands (which secrete PARATHYROID hormone). Develops from the base of the pharynx and sits just above the trachea

Question 2

what is the thyroid full of

Answer 2

follicular cells, colloid, parafollicular cells.

Question 3

what are parafollicular cells

Answer 3

found between the follicles

Question 4

what is the colloid

Answer 4

proteinaceous substance found inside the follicles. it is a massive store of iodothyronines

Question 5

what are the follicular cells

Answer 5

the cells lining the follicle

Question 6

List the main hormones produced by the follicular and parafollicular cells of the thyroid

Answer 6

the parafollicular cells produce calcitonin. Follicular cells produce iodothyronines

Question 7

describe the synthesis of iodothyronine

Answer 7

Iodide in the cell diffuses down to apical membrane and enters the colloid via the Pendrin pump. Thyroid peroxidase (TPO) - in the presence of hydrogen peroxide - converts iodide into a reactive iodine form. Tyrosyl residues in the thyroglobulin become iodinated by the reactive iodine. This results in the production of Mono and Diiodothyronines (MIT and DIT) attached to the thyroglobulin. TPO catalyses the coupling reactions of MIT and DIT by altering the configuration of their amino acid chains. Leads to esult of this is either Triiodothyronines (T3) or Tetraiodothyronines (T4) being formed.

Question 8

The effects of TSH (Thyrotrophin/ Thyroid Stimulating Hormone) on iodothyronine production

Answer 8

TSH binds to the TSHR receptor, it stimulates the Iodide pump to pump iodide into the follicular cell and then iodide is pumped out of the cell via the Pendrin pumps. TSH acts as a TF and stimulates thyroglobulin production. TSH causes TPO to migrate to colloid and take part in iodination. TSH causes Thyroperoxidase to migrate to colloid and take part in coupling reaction. TSH stimulates migration of lysosomes to apical membrane and stimulates the uptake of colloid by the apical membrane. The internalised colloid fuses with the lysosome and the enzymes break down the protein, liberating T3 and T4 which move enter the blood

Question 9

where are thyrotrophin receptors found

Answer 9

basal membrane

Question 10

What is the role of thyroglobulin in iodothyronine production

Answer 10

A globular protein that is a long chain of amino acids consisting of many tyrosines aka tyrosyl residues. Reactive iodine incorporates into the tyrosyl residues It moves through the aprical membrane into the colloid.

Question 11

What do iodide pumps do

Answer 11

pump iodide into the follicular cells from the blood

Question 12

iodothyronine storage

Answer 12

There is enough iodinated TG stored within the colloid to provide enough iodothyronines for several weeks in the absence of dietary iodine. Necessary as the level of iodine in one’s diet fluctuates and is unpredictable. Thyroid is unique amongst endocrine glands as it can store its hormone.

Question 13

How is Iodothyronine released

Answer 13

The T3-TG-T4 complex is engulfed by the colloid membrane and moves back into the follicular cell where it encounters lysosomes which proteolyse the TG leaving just T3 and T4. T3 and T4 are then excreted into blood by exocytosis

Question 14

What is the latent period of T3

Answer 14

12 hours. It has a very long time before having an effect

Question 15

what is the latent period of T4

Answer 15

72 hours. It has a very long time before having an effect

Question 16

what is the half life of T3

Answer 16

2 days

Question 17

what is the half life of T4

Answer 17

7-9 days

Question 18

what is thyroxine

Answer 18

T4

Question 19

How are iodothyronines transported

Answer 19

Iodothyronines are transported in the blood bound to plasma proteins. Thyroxine-binding globulin (TBG) is specific to T3 and T4. Albumin is the most common of the plasma proteins and isn’t specific but T3 and T4 can loosely bind to albumin. Prealbumin binds a fair amount of T4 but very little T3.

Question 20

What is prealbumin also known as

Answer 20

Transthyretin

Question 21

What are the bioactive iodothyronines

Answer 21

the free molecules which are not bound to plasma proteins

Question 22

why are iodothyronines transported by plasma proteins

Answer 22

to prevent uptake by non-target cells

Question 23

Describe the deiodination of Thyroxine

Answer 23

T4 can be deiodinated in target tissues to produce T3 which is more bioactive. T4 can be deiodinated in a different position to form reverse T3 (rT3) which is biologically inactive. In situations where you want reduced metabolism (e.g. starvation) then T4 tends to be converted to rT3 rather than T3

Question 24

what is the main hormone product of the thyroid gland

Answer 24

T4

Question 25

What are the physiological actions of iodothyronines

Answer 25

Increase the Basal Metabolic Rate. Increase carbohydrate, fat and protein metabolism. Important role in fetal development. Enhance the effects of catecholamines. Interact with other endocrine systems. Have effects on the CNS. Increases vitamin C synthesis from retinal.

Question 26

Iodothyronines - increase basal metabolic rate (what does this result in)

Answer 26

Occurs in most peripheral tissues (not brain) which results in calorigenesis (heat generation). Important in body temperature regulation

Question 27

Iodothyronines - Increase carbohydrate, fat and protein metabolism (what is this important for)

Answer 27

This is important for normal growth and development. The iodothyronines affect both anabolic and catabolic processes depending on the state of the thyroid.

Question 28

Iodothyronines - important for fetal development (why is it important)

Answer 28

Lack of iodothyronines is practically irreversible and causes a condition known as cretinism. Thyroid hormone levels are measured in the heel-prick test (test for congenital hypothyroidism). This is because T3 and T4 exert effects on formation of axon terminals, the production of synapses and the growth of dendrites and their spines.

Question 29

Iodothyronines - enhance the effects of catecholamines (what does this lead to)

Answer 29

Stimulate cells to produce catecholamine receptors.

This can lead to as tachycardia, glycogenolysis and lipolysis. Fight or flight response. Sympathetic.

Question 30

Iodothyronines - interact with other endocrine systems (what hormones does it interact with)

Answer 30

There is an important interaction between iodothyronines and oestrogens

Question 31

Iodothyronines - has an effect on the CNS

Answer 31

It helps the formation of myelin so one can see how a lack of the iodothyronines would cause severe problems in the CNS and thus mental retardation. Important in brain development. It also increases Vitamin A.

Question 32

Iodothyronines - increases vitamin C synthesis from retinal

Answer 32

Hypothyroidism leads to build up of retinal in the blood leading to yellowish skin coloration

Question 33

Explain the mechanisms of action of the iodothyronines.

Answer 33

Iodothyronines can enter the target cell readily so interact with intracellular TR receptors. The receptor-hormone complex stimulates transcription and so increases protein synthesis . It also increases membrane transport mechanisms in the brain. Increases metabolic activity in the mitochondria.

Question 34

what kind of action do Iodothyronines have

Answer 34

genomic action

Question 35

Describe the control mechanisms that inhibit iodothyronine production

Answer 35

Thyrotrophin/TSH release from the adenohypophysis has an auto negative feedback loop on the hypothalamus, so TRH is not released. Iodothyronines released from the thyroid also have negative feedback loops: They have a direct inhibition on adenohypophysis and indirect inhibition on hypothalamus so TRH is not released. Somatostatin and Glucocorticoids inhibit TRH release from the adenohypophysis. Ingestion of large amounts of inorganic iodide (Wolff-Chaikoff Effect) and sympathetic innervations of the thyroid.

Question 36

Describe the hypothalamo-pituitary-thyroidal axis

Answer 36

Neurones originating rom the hypothalamus release Thyrotrophin Releasing Hormone (TRH) into the primary capillary plexus. TRH passes down the portal vessels to the adenohypophysis where it’ll bind to membrane receptors. TRH will work on thyrotrophs to produce thyrotrophin/TSH. Thyroid gland releases iodothyronines (T3 and T4)

Question 37

Describe the control mechanisms that stimulate iodothyronine production

Answer 37

Oestrogen and Thyroid Releasing Hormone (the main factor) stimulate TRH release.

Question 38

What does having good sympathetic innervation of the vasculature mean?

Answer 38

it is possible that by altering the blood flow through the thyroid you could have some control over the production of T3 and T4

Question 39

What is thyrostimulin

Answer 39

a recently discovered 2-unit glycoprotein. Found in adenohypophysis (and other tissues e.g. heart, adipose, gonads). Binds to the Thyrotrophin Receptor.
Functions are unknown (could be a paracrine mechanism)