The Thyroid Gland and the Iodothyronines (6) Flashcards
describe the structure of the thyroid gland
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
what is the thyroid full of
follicular cells, colloid, parafollicular cells.
what are parafollicular cells
found between the follicles
what is the colloid
proteinaceous substance found inside the follicles. it is a massive store of iodothyronines
what are the follicular cells
the cells lining the follicle
List the main hormones produced by the follicular and parafollicular cells of the thyroid
the parafollicular cells produce calcitonin. Follicular cells produce iodothyronines
describe the synthesis of iodothyronine
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.
The effects of TSH (Thyrotrophin/ Thyroid Stimulating Hormone) on iodothyronine production
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
where are thyrotrophin receptors found
basal membrane
What is the role of thyroglobulin in iodothyronine production
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.
What do iodide pumps do
pump iodide into the follicular cells from the blood
iodothyronine storage
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.
How is Iodothyronine released
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
What is the latent period of T3
12 hours. It has a very long time before having an effect
what is the latent period of T4
72 hours. It has a very long time before having an effect
what is the half life of T3
2 days
what is the half life of T4
7-9 days
what is thyroxine
T4
How are iodothyronines transported
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.
What is prealbumin also known as
Transthyretin
What are the bioactive iodothyronines
the free molecules which are not bound to plasma proteins
why are iodothyronines transported by plasma proteins
to prevent uptake by non-target cells
Describe the deiodination of Thyroxine
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
what is the main hormone product of the thyroid gland
T4
What are the physiological actions of iodothyronines
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.
Iodothyronines - increase basal metabolic rate (what does this result in)
Occurs in most peripheral tissues (not brain) which results in calorigenesis (heat generation). Important in body temperature regulation
Iodothyronines - Increase carbohydrate, fat and protein metabolism (what is this important for)
This is important for normal growth and development. The iodothyronines affect both anabolic and catabolic processes depending on the state of the thyroid.
Iodothyronines - important for fetal development (why is it important)
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.
Iodothyronines - enhance the effects of catecholamines (what does this lead to)
Stimulate cells to produce catecholamine receptors.
This can lead to as tachycardia, glycogenolysis and lipolysis. Fight or flight response. Sympathetic.
Iodothyronines - interact with other endocrine systems (what hormones does it interact with)
There is an important interaction between iodothyronines and oestrogens
Iodothyronines - has an effect on the CNS
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.
Iodothyronines - increases vitamin C synthesis from retinal
Hypothyroidism leads to build up of retinal in the blood leading to yellowish skin coloration
Explain the mechanisms of action of the iodothyronines.
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.
what kind of action do Iodothyronines have
genomic action
Describe the control mechanisms that inhibit iodothyronine production
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.
Describe the hypothalamo-pituitary-thyroidal axis
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)
Describe the control mechanisms that stimulate iodothyronine production
Oestrogen and Thyroid Releasing Hormone (the main factor) stimulate TRH release.
What does having good sympathetic innervation of the vasculature mean?
it is possible that by altering the blood flow through the thyroid you could have some control over the production of T3 and T4
What is thyrostimulin
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)
