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In this video, we’re going walk through the thyroid hormone synthesis pathway step-by-step.
A lot of these steps involve hormones or enzymes that are
used to diagnose and treat thyroid conditions.
So knowing these steps will be helpful.
By the end of the video, you’ll know everything in the chart.
We’re going to come back to the chart at the end, so make sure to watch the entire video.
All of the steps along with the chart can be found
in the lecture notes and study guide on our website linked down below.
I highly recommend checking out the lecture notes because they easily
walk you through step-by-step everything we’re going to talk about in this video.
All of the videos come with lecture notes and study guides,
so make sure to subscribe to the channel to not miss out on those.
There are 3 main structures involved in thyroid hormone regulation and synthesis.
They include the hypothalamus, anterior pituitary gland, and thyroid gland.
The 3 structures communicate and work together to produce and regulate thyroid hormone.
Together they’re called the hypothalamic-pituitary-thyroid axis,
or HPT axis for short.
The HPT axis is a self-regulatory circuit
that balances thyroid hormone levels in the blood and maintains thyroid homeostasis in the body.
The pathway begins with the hypothalamus, followed by the anterior pituitary gland,
and ends with the thyroid gland.
The easy way to remember the order of the 3
structures involved is to go in alphabetical order.
We have the “H” for hypothalamus, the “P” for pituitary gland, and the “T” for thyroid gland.
Let’s take a closer look at what’s going on in
each structure starting with the hypothalamus and pituitary gland.
Here you can see we have zoomed in on the hypothalamus and the pituitary gland.
The hypothalamus is located deep in the brain below the thalamus.
The pituitary gland is located below the hypothalamus,
and it’s the anterior pituitary gland that will be important in this video.
Let’s start with the hypothalamus.
There are neurons located in the hypothalamus
that have the ability to secrete hormones onto the anterior pituitary gland.
One of these groups of neurons is called the paraventricular nucleus (PVN).
The paraventricular nucleus secretes a hormone called thyrotropin-releasing hormone, or TRH.
This TRH release from the hypothalamus is the first main step in our pathway.
TRH will then travel to the anterior pituitary gland through the hypophyseal portal system,
which are the blood vessels connecting the hypothalamus and anterior pituitary gland.
TRH will then stimulate cells in the anterior pituitary gland called thyrotropes.
When the thyrotropes are stimulated by TRH,
they will release another important hormone called thyroid-stimulating hormone, or TSH.
TSH release from the anterior pituitary gland is the second main step of our pathway.
Once TSH is released from the anterior pituitary gland, it then enters the bloodstream
where it travels to another gland located in the neck.
This gland is called the thyroid gland,
which is a butterfly shaped structure located at the base of the anterior neck.
TSH will stimulate the thyroid gland to produce thyroid hormone.
Before we talk about how thyroid hormone is actually synthesized,
let’s go back to our original diagram quick and recap everything so far.
So we said there are 3 main structures involved in our pathway.
They include the hypothalamus, anterior pituitary gland, and thyroid gland.
The pathway starts with the hypothalamus.
The hypothalamus releases a hormone called thyrotropin-releasing hormone or TRH.
TRH stimulates the anterior pituitary gland to release another hormone
called thyroid-stimulating hormone or TSH.
TSH is released from the anterior pituitary gland into the bloodstream.
TSH circulates in the blood and binds to the thyroid gland.
This stimulates the thyroid gland to synthesize thyroid hormone.
Thyroid hormone is then released from the thyroid gland into the bloodstream
where it acts on many different tissues and organs in the body.
We’re going to see that main thyroid hormones
are triiodothyronine which is T3 and thyroxine which is T4.
One more trick to help you remember TRH and TSH
because it can be easy to mix them up or forget which one comes first.
You can remember these by going in alphabetical order as well.
Use the “R” in TRH and the “S” in TSH.
“R” comes before “S” which will help you remember the releasing hormone or TRH comes first,
followed by the stimulating hormone or TSH.
Now that we understand the hypothalamus and anterior pituitary gland,
let’s take a closer look at how thyroid hormone is synthesized in the thyroid gland.
Here you can see we have zoomed in on the thyroid gland.
The thyroid gland is made up of follicles which are the
structural and functional units of the thyroid.
The follicles are lined by follicular cells, which are also known as thyrocytes,
and the lumen or center of the follicle is filled with a substance called the colloid.
The thyroid gland is very vascular and filled with blood vessels.
The TSH that is released from the anterior pituitary gland
will travel through the bloodstream and bind to thyroid follicular cells.
This will stimulate the thyroid gland to produce thyroid hormone.
Let’s now take a closer look at how thyroid hormone is synthesized within the follicles.
Here you can see we have zoomed in on a follicle and we’re looking at a blood vessel in red,
with a follicular cell in brown above it, and above that we have the lumen or colloid.
Let’s go step-by-step on how thyroid hormone is produced within the thyroid gland.
First we said the TSH released from the anterior pituitary gland circulates in the bloodstream.
TSH will then bind to TSH receptors on the follicular cells of the thyroid.
Once TSH binds to TSH receptors,
this will stimulate or enhance the production of an important protein made by the follicular cells.
This protein is called thyroglobulin.
Thyroglobulin is then released into the colloid.
So the colloid is very rich in thyroglobulin.
We’re going to see shortly that thyroglobulin is the precursor for thyroid hormone.
However, there is one more ingredient we need from the blood to make thyroid hormone,
and that’s iodide.
Try not to confuse iodide and iodine because we’re going to be talking about both.
We mainly get iodine from our diet and then it gets absorbed into the bloodstream as iodide.
TSH will not only enhance thyroglobulin production,
but it also stimulates the uptake of iodide from the blood into the follicular cell.
The concentration of iodide is greater in the follicular cells than the blood, so iodide can’t
move by itself into the cell because it would be moving against its concentration gradient.
So iodide gets help from sodium and uses a sodium/iodide symporter to get into the cell.
Once iodide is in the follicular cell it will
enter the colloid through a transporter called pendrin.
Now that iodide is inside the lumen of the follicle,
the thyroid is picky and wants iodine not iodide.
So it uses an enzyme called thyroid peroxidase, or TPO to convert iodide into iodine.
This process is known as iodide oxidation because we are losing electrons to form iodine.
Now we have our 2 ingredients to make thyroid hormone.
We have thyroglobulin.
And we have iodine.
Now it’s time to combine those 2 ingredients.
As we mentioned before, thyroglobulin is a protein.
And we know proteins are made of amino acids.
Thyroglobulin contains tyrosine amino acids.
The thyroid will again use the enzyme thyroid peroxidase to place iodine onto the tyrosine.
This process is called organification or iodination of thyroglobulin.
We know from our medical terminology video that the prefix “mono” means one and “di” means two.
So if one iodine is placed on tyrosine, then it becomes monoiodotyrosine or MIT.
If two iodine are placed on tyrosine, then it becomes diiodotyrosine or DIT.
The MIT and DIT molecules
then get combined to make T3 and T4, which are the main thyroid hormones.
Let’s see how this works.
If we combine one DIT which has 2 iodine with one
MIT which has 1 iodine, then we will have 2 + 1 which equals 3 iodine.
This will give us T3, also known as triiodothyronine.
If we combine two DITs which each have 2 iodine, then we will have 2 + 2 which equals 4 iodine.
This will give us T4, also known as thyroxine or tetraiodothyronine.
The process of combining MIT and DIT molecules to form T3 and T4 is known as coupling.
And guess what enzyme it uses again?
It uses thyroid peroxidase.
This makes it really easy to remember because we’re using the same enzyme for all these steps.
We don’t have to remember a bunch of different enzymes.
So we can see thyroid peroxidase has 3 important roles.
First, it’s involved in oxidation where we turn iodide into iodine.
Second, it’s involved in iodination where we added iodine to thyroglobulin,
specifically the tyrosine amino acids.
Third, it’s involved in coupling the DITs and MITs
to form T3 and T4, which are the main thyroid hormones.
And the cool thing is TSH will also increase the activity of thyroid peroxidase,
so we can see how this is all tying together.
So now our thyroglobulin has T3 and T4 in it,
Which will enter back into follicular cell through a process called endocytosis.
From there we have to cut the T3 and T4 out of the thyroglobulin,
and we do that using a proteolytic enzyme called protease.
T3 and T4 now enter the bloodstream to act on target tissues and organs.
The majority of T3 and T4 travel through the blood bound to a protein
called thyroxine-binding globulin or TBG.
So now you can see how thyroid hormone is synthesized.
I know this was a lot of information, so remember there is a great step-by-step
explanation in our lecture notes of everything we just talked about.
It’s linked down below, so make sure to check that out.
It will help bring everything together if you need to review this more.
I also put together this summary to help make it easier for you.
It summarizes all the main steps of thyroid hormone synthesis that we talked about.
This chart can also be found in the lecture notes and study guide linked down below.
Those lecture notes will walk you through each of these steps.
We’re also going to see in future videos when we talk about thyroid conditions
how things like TRH, TSH, T3, T4, thyroglobulin,
and thyroid peroxidase are all important players in diagnosing and treating those conditions.
Hopefully this gave you a better understanding of thyroid hormone synthesis.
Remember you can find the step-by-step explanations of everything we talked about
in the lecture notes and study guide on our website linked down below.
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