6- The Thyroid And Iodothryonides Flashcards
Describe the structure of the thyroid gland
Location: top of trachea
• Bi-lobed
• ISTHMUS = the bit of tissue that joins together the two lobes
• PYARMID = the bit of tissue on the top of the isthmus which is present in some
people (important clinically because a thyroid tumour could be in the pyramid)
• Thyroid is full of follicles
• Follicular cells = the cells lining the follicle
• Colloid = proteinaceous substance found inside the follicles
• Parafollicular Cells = found between the follicles and they also provide
hormones
How are iodothyronines s produced by follicular cells
Thyrotrophin Receptors are found on the serosal/basal membrane
• Iodide must be pumped into the cell from the blood via IODIDE PUMPS (sodium iodine symporter)
• The thyroid hormones are produced on the apical membrane and so iodide needs to be pumped out into the colloid by PENDRIN PUMPS
TSH binds to the receptor, it stimulates the Iodide pump to pump iodide into the cell and then iodide is pumped out of the cell via the Pendrin pumps
• TSH also affects the nucleus and stimulates the synthesis of THYROGLOBULIN
• The thyroglobulin is also moved into the colloid and remains associated with
the apical membrane
• TSH also stimulates THYROID PEROXIDASE (TPO) enzyme
• TPO - in the presence of hydrogen peroxide it converts iodide into a reactive
iodine form which is very short lived
• Thyroglobulin is a long array of amino acids which have a certain number of
TYROSYL RESIDUES which become iodinated by the reactive iodine
• The tyrosyls can be iodinated in one or two positions to form
MONOIODOTYROSINE (MIT) and DIIODOTYROSINE (DIT)
• TSH keeps stimulating TPO which allows COUPLING REACTIONS to take place
where Triiodothyronines (T3) and Tetraiodothyronines (T4) can be formed
• The colloid is a massive store of iodothyronines
• TSH then stimulates lysosomes to move towards the apical membrane and
stimulates the uptake of colloid by the apical membrane
• The colloid that has been internalised then fuses with the lysosome and the
enzymes break down the protein, liberating T3 and T4 which can then move out in to the blood
How is iodothryonine transported in the blood
Tends to be transported by Plasma Proteins to prevent uptake by non-target
cells
• Globulins tend to be SPECIFIC to a particular molecule
• Iodothyronines are transported in the blood MOSTLY bound to plasma
proteins:
(70%) THYROXINE-BINDING GLOBULIN (TBG) is specific to T3 and T4
10% Albumin - the most common of the plasma proteins - isn’t specific but T3 and T4 can loosely bind to albumin
Prealbumin - binds a fair amount of T4 but very little T3
The BIOACTIVE iodothyronines are the FREE MOLECULES which are NOT bound to plasma proteins: 0.05% t4, 0.5% t3
Describe deiodination of thyroxine
T4 is the main hormone product of the thyroid gland
• But T3 is the more active of the two
• 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
Describe the 2 main types of Action of Iodothyronines 1
• INCREASE BASAL METABOLIC RATE
Almost all tissues react this way except the BRAIN
Important in calorigenesis (secondary increase in heat production) Important in body temperature regulation
• INCREASE PROTEIN, CARBOHYDRATE AND FAT METABOLISM
Stimulates metabolism in BOTH directions (anabolic and catabolic) Important for normal growth and development
How is TH important in development
Important role in foetal growth and development
• Lack of iodothyronines can lead to CRETINISM if untreated within a few months
• Thyroid hormone levels are measured in the heel-prick test
Name some further effects of Iodothyronines
ENHANCE THE EFFECTS OF CATECHOLAMINES
This can lead to tachycardia, glycogenolysis and lipolysis
• INTERACT WITH OTHER ENDOCRINE SYSTEMS
There is an important interaction between iodothyronines and
oestrogens
• HAVE EFFECTS ON THE CNS, Gi, reproductive systems (basically all organ systems)
INCREASES VITAMIN C SYNTHESIS FROM RETINAL
Hypothyroidism leads to build up of retinal in the blood leading to yellowish skin coloration
Describe the half life and latent period of THs
Latent Periods T3 = 12 hours T4 = 72 hours T3 is more rapid acting • Biological Half-Lives T3 = 2 days T4 = 7-9 days
What can a high iodide dose cause
Wolff- chaikoff effect (inhibited TH release)
Describe possible mechanisms of action of iodothyronines
Iodothyronines can enter the target cell readily so interact with intracellular receptors
• The receptor-hormone complex will have its effect in the nucleus which leads to new proteins being synthesised (e.g. enzymes)
• It also affects membrane transport pumps in the brain
• Stimulates metabolic activity so has a lot of effects on the mitochondria
• IMPORTANT: Iodothyronines have a GENOMIC ACTION
Describe how the release of TRH has effects on the follicular calls of the thyroid
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 (NOTE: TRH is a glycoprotein)
• TRH will work on thyrotrophs to produce thyrotrophin
• Thyrotrophin then has lots of effects on the follicular cells in the thyroid
Describe how iodothyronine production is increase and decreased
INCREASES IODOTHYRONINE PRODUCTION: Thyroid Releasing Hormone Oestrogens • DECREASES IODOTHYRONINE PRODUCTION: T3/T4 • Directly on adenohypophysis • Indirectly on hypothalamus Somatostatin Glucocorticoids Ingestion of large amounts of inorganic iodide (Wolff-Chaikoff Effect) Thyrotrophin - auto-negative feedback loop to the hypothalamus
