Thyroid and iodothyronines Flashcards
What is the anatomy of the thyroid gland?
Located at the top of the trachea.
Bi lobed- at the centre is the isthmus (the tissue that joins the two lobes together)
Pyramidal lobe is a bit of tissue on top of the isthmus which is present in some people.
There are follices present in the thyroid lobes and follicular cells line the follicles.
Colloid- proteinaceous substance found inside the follicles (at the centre)
Parafollicular cells are found between the follicles and they also provide hormones (calcitonin)
With respect to follicular cells, which side is the basolateral/ apical membrane facing?
The apical membrane faces inwards- towards the colloid
The basolateral membrane faces outwards- faces the blood (vessel)
Where does the iodine come from and how does it get into the follicular cell?
Iodide is taken up from the blood by special iodide pumps found on the basolateral membrane of the follicular cell.
Once the iodide is in the follicular cell, where does it migrate to and why?
The iodide enters through the basolateral membrane but migrates to the apical membrane because thyroid hormones are produced on the apical membrane.
Therefore, iodide is pumped out into the colloid by PENDRIN PUMPS
What else is found on the basolateral membrane? And what are the effects once binding occurs?
Thyrotropin receptors are found on the basolateral membrane.
TSH travelling in the blood will bind to this receptor. This action will stimulate the iodide pump and iodide will be pumped into the cell.
As this happens, the iodide will be pumped out of the cell into the colloid by the pendrin pump.
What are the other effects of TSH inside the follicular cell?
- TSH affects the nucleus and stimulates the synthesis of THYROGLOBIN- the thyroglobin is moved to the colloid and remains associated to the apical membrane
- TSH stimulates the enzyme thyroid peroxidase (TPO). TPO will convert iodide to iodine in the presence of hydrogen peroxide. Also on the apical membrane. TSH will continue to stimulate TPO which allows coupling reactions to occur in order (in order to form T3 and T4)
- TSH will stimulate lysosymes to move towards the apical membrane and stimulate uptake of the colloid by the apical membrane. Enzymes breakdown the protein, liberating the T3 and T4 which can move out into the blood.
What are the sequence of events after TSH stimulates TPO (thyroid peroxidase)?
TPO converts iodide into iodine in the presence of hydrogen peroxidase.
Thyroglobuin (protein that the nucleus is stimulated to make) is a long array of amino acids which have a certain number of tyrosine residues- they become iodinated by the active iodine. Iodination can happen in one or two positions to produce MIT (monoiodotyrosine) or DIT (diiodotyrosine).
TSH will continue to stimulate TPO which will allow for coupling reactions. This will take place where triiodotyrosine (T3) and tetreiodotyrosine (T4) can be formed.
Lysosomes take the thyroglobulins from the colloid and there are enzymes inside there which break it down to T3 and T4.
What is iodinated in thyroglobulin (TG) protein?
There are tyrosine amino acids in the chain. The tyrosyl residues that are incorporated in the chain are iodinated either in one or 2 places, producing MIT or DIT.
Depending on how they join up, you produce T3 or T4
Position one is where the extension comes out and iodination can happen at the 3 or 5 position.
How is iodothyronine (t3 and t4) transported?
They are mainly bound to plasma proteins to prevent uptake by non-target cells.
The proteins include:
- Thyroid-binding globulins (TBGs)- 70-80%. Globulins are specific to T3 and T4
- Albumin (10-15%)- most common of the plasma proteins but is not specific to T3 and T4- loosely binds
- Prealbumin (aka transthyretin)- binds a fair amount of T4 but very little T3
NB- bioactive iodothyronines are free molecules which are not bound to plasma proteins. Only 0.05% T4 and 0.5% T3 are unbound
What are the latent periods and half-lives of the iodothyronines?
Latent periods:
T3= 12 hours
T4= 72 hours
T3 is more rapidly acting- biological half lives:
T3= 2 days
T4= 7-9 days
What is the deiodination of thyroxine?
BTW!!! T4= thyroxine
T3= thyronine
T4 (thyroxine) is the main product of the thyroid gland and it can be deiodinated in target tissues to form T3 (thyronine). T3 is the more active of the two and it is more bioactive.
T4 is deiodinated in a different positon to form REVERSE T3 (rT3) which is biologically inactive.
In situations when you want reduced metabolism, T4 tends to be converted into rT3 instead of T3.
This process just kind of prevents T4 from having an over effect (just like muting it a little).
Type 1 iodothyronine actions
Fetal growth and development- lack of iodothyronines can lead to cretinism if untreated- tested with the heel prick (TH and TSH are measured in the new-born’s blood).
This is congenital hypothyroidism
Type 2 iodothyronine actions
Increase in basal metabolic rate (BMR) (except the brain).
Increase in protein, carbohydrate and fat metabolism- stimulated in both directions, catabolic and anabolic.
Enhance in the effect of catecholamines- this can lead to tachycardia, glycogenolysis and lipolysis
Interaction with other endocrine systems- there is an important interaction between iodothyronines and oestrogens
There are affects on the CNS- important for brain development.
Increase in vitamin c synthesis from retinal- hypothyroidism leads to build up of retinal blood leading to yellow skin colouration.
How do T3 and T4 have effects on their target cell?
T3 and T4 enter cells, T4 can be deiodinated into T3.
On entering, they will interact with intracellular receptors. The receptor hormone complex will have its effect in the nucleus which leads to new proteins being synthesised (like enzymes)… iodothyronines have a GENOMIC ACTION
It also affects membrane proteins mechanisms (transport pumps) in the brain.
Metabolic activity is stimulated as it has affects in the mitochondria.
How is TH produced ( in terms of hypothalamus and pituitary gland)?
Neurones in the hypothalamus release thyrotropin releasing hormone (TRH) into the primary capillary plexus.
TRH passes down the portal vessels into the adenohypophysis where it will bind to the membrane receptors.
The TRH will work on the thyrotrophs cells in the anterior pituitary gland to produce thyrotrophin (TSH).
TSH will have many effects on the follicular cells in the thyroid.
How is iodothyronine production controlled?
NEGATIVE FEEDBACK
T3 and T4 stimulate the changes
For an increase in iodothyronine production: TRH increase and oestrogen too (has affect on the thyrotroph cell)
For a decrease in iodothyronine production- T3 and T4 can either directly act on the adenohypophysis (glucocorticoids) or indirectly on hypothalamus (somatostatin).
Ingestion of large amounts of large amounts of iodide (wolff-Chaikoff effect)- changes in the thyroid gland so less T3 and T4 is produced
