Lecture notes
Thyroid hormones
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- Aston University, Birmingham (Aston)
In depth cell signalling and physiology notes, created using synchronous and asynchronous material.
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Thyroid hormones.Hormones of thyroid.
TRH- thyrotropin-releasing hormone. – this refers to the releasing hormone that
comes from the hypothalamus, and stimulates the thyrotropes, which are the cells in
the anterior pituitary to release TSH
TSH- thyroid stimulating hormone. -TSH gets released by the thyrotropes, in the
anterior pituitary. We use TSH diagnostically when we diagnose hypo or hyper
thyroidism.
These 4 hormones are the thyroid hormones themselves and they are built on a
tyrosine backbone, so they are built by adding molecules to molecules.
MIT- monoiodotyrosine. – involved in the production and does not get released and
does not have biological action
DIT-diiodotyrosine. – involved in the production and does not get released and does
not have biological action.
T3-triiodothyronine.
T4-thyroxine (tetraiodothyronine)
Iodination is a really important part of activation of thyroid hormones.
Other molecules that are important:
TG- thyroglobulin, this is a backbone which is used to produce thyroid hormones.
TBG- thyroid binding globulin, this is a molecule which binds thyroid hormone. There
are free and bound hormones, if the hormone is circulating in the blood bound to
something, such as a binding protein, it will not be active because it will not be able
to activate its receptor. However, if it is a free hormone, so it is released from a bind
protein that it is circulating with, it can be active. The levels of thyroid binding
globulins are important because they will directly correlate with the levels of free
thyroid hormones.
D1-D3- deiodinases, these enzymes remove iodides from molecules, either activating
or inactivating, therefore their activity and expression is important because the
relative levels of T3 and T4, and therefore free T3 and T4 (not bound) are really
important when it comes to how effective your thyroid hormones are at doing their
job.
TR- thyroid receptor, a hormone is a chemical messenger which has an impact on a
cell, via a receptor specific mechanism. Thyroid hormones are not peptide
hormones, they are not steroid hormones. They are cell- permeable and this means
that they do not need a plasma membrane receptor because they can cross the cell
membrane. Therefore, the thyroid hormone receptor is found inside the cell, and it
co-binds the retinoic X receptor, which is a co-regulator of expression.
RXR retinoid x receptor- Generally you need thyroid receptor and a retinoic X
receptor to see the effects of thyroid hormones, which normally occur via gene
transcription.
Thyroid gland: composed of follicles.
The thyroid gland has a structure of two lobes which are connected by a bridge
of endocrine tissue, and if you take a cross section of this, there are fluid filled
gaps called follicles.
, Follicles contain a protein rich aqueous solution known as colloid and it is within
this that we can see processes and production of thyroid hormones happening.
Colloid containing follicles are surrounded by follicular cells, these are also
involved in the process of production of thyroid hormone.
This is where we see the 4 thyroid hormones produced and released from.
Thyroid hormone structures.
Tyrosine which is the backbone for production of thyroid hormones is iodinated.
Depending on where and how many iodide molecules and tyrosine molecules are
produced we have different hormones.
In the case of 2 tyrosine molecules iodinated in 3 positions we would have T3
(triiodothyronine).
In the case of 2 tyrosine molecules, iodinated in 4 positions, we have the most active
form of thyroid hormones, thyroxine (T4).
Activity of thyroid hormones is related specifically to how much iodination has
occurred to them.
Therefore, there is an element of control, because T4 is more active than T3.
Action of TSH on the thyroid.
TSH is the hormone that is released by the anterior pituitary that tells the thyroid
gland to make thyroid hormones.
It is a major controller therefore of not just thyroid hormone production but also the
growth of thyroid hormone cells.
Mutations in the receptor for TSH can lead to thyroid disorders, such as
hyperthyroidism, this means excess thyroid hormones are being produced.
The TSH receptor is a G-protein receptor, it has two subunits, the alpha subunit
which binds TSH and the beta subunit which is where we see signal transduction
activated and specifically it is a Gs/Gq associated GPCR.
Thyroid hormone synthesis
THS has been released, it is bound to our THS receptor, it has led to the process of
thyroid hormone synthesis.
First iodide is co-transported (pendrin) along with sodium via an iodide sodium co-
transporter, from the interstitial fluid into the follicle cells. These are the cells that
surround the colloid.
The iodide diffuses passively across the follicle cell, and then it is transported into
the colloid.
It is then oxidised and attached to the tyrosine rings, which make up the backbone
for our thyroid hormones.
We also have a molecule of thyroglobulin which holds tyrosine rings together whilst
thyroid hormones are being produced.
The iodinated ring of one monoiodotyrosine or diiodotyrosine is added to a
diiodotyrosine and that makes either T3 or T4.
If you add together an MIT and a DIT, you get T3.
If you add together DIT and another DIT, you get T4.
Adding together mono or di iodo tyrosine molecules makes up T3 or T4.
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