Lecture notes
Thyroid hormone signalling
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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 hormone signalling.How are thyroid hormones made?
Thyroid hormones are made from the amino acid tyrosine.
Tyrosine is modified by the addition of the iodine groups. (Tyrosine is iodinated).
This forms two different forms of the thyroid hormone: thyroxine (T4) or
triiodothyronine (T3).
Thyroid hormone is not a peptide hormone or a signalling hormone it is an amino
acid hormone.
Thyroid hormone signalling pathway.
Thyroid hormone needs to cross the hydrophobic cell membrane to cross the cell.
Thyroid hormones are hydrophobic so they can readily cross the cell membrane.
Thyroid hormones can also be transported via specialist membrane transporters.
The presence of the transporters gives us a way of regulating thyroid hormone
signalling.
This is because the expression of the membrane transporters, is regulated both in
space, so they are expressed in high levels ion certain tissues, we can also regulate
their expression over time, for example, especially during foetal development, we
can see high levels of these transporters are in expressed in certain tissues at certain
points.
This means that we can control thyroid hormone signalling at the level at which the
thyroid hormone can enter the cell by changing where and when these membrane
transporters for the thyroid hormone are expressed.
Once the thyroid hormone has entered the cell, we see local activation.
The T4 form of thyroid hormone is less active than the T3 form.
So once T4 enters the target cell it can be converted to T3 through the activity of the
deiodinases enzymes (D1/D2).
T4 is converted to T3 through the activity of D1/D2 deiodinases but it can also be
converted into an inactive form of T3 called reverse T3 (rT3), by the type 3 5-
deiodinase (D3) enzyme.
The activity of the deiodinase enzymes is highly regulated, they can be ubiquinated
on certain lysine residues and the ubiqitation targets them for degradation via the
proteosome.
Thyroid hormone needs a receptor to function, the receptor for thyroid hormone is
the thyroid hormone receptor (THR).
There are multiple isoforms for this receptor, but they are all expressed from a single
thyroid hormone receptor gene.
All the isoforms are members of a superfamily of receptors called the nuclear
hormone receptors.
Although there are multiple isoforms, they do share some common sequences, or
functional domains.
They all contain a region that allows them to bind directly to the DNA and they all
contain a region that allows them to bind to T3.
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