INSTRUCTOR: Hello and welcome to the Penguin Prof Channel.
In today's episode, I'd like to talk about how to approach
endocrinology for your physiology classes as well as for a lot of medical exams.
We are going to get through this table in
a way that makes sense so you don't have to memorize
it, because you're going to need it guys for all of these exams and a whole lot more.
As always, I'm going to ask for your support.
If you could take just a second and click those buttons if you find these videos helpful,
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Some knowledge that I'm assuming here:
knowledge about polar molecules and how they interact with the cell membrane.
If you want to know more about the structures,
the chemical structures, I'm going to show I have a video there.
This one is probably the most important: signal transduction.
I am assuming that you understand a little bit about how ligands and receptors work.
As always, I have the links down below.
Now we are talking about an aspect of
cell-cell communication when we talk about endocrinology.
But to take a step back for just a second,
cells can communicate with other cells that are close by with
gap junctions and contact dependent signals and paracrine and autocrine secretions.
For long distance communication,
we've got a couple of options.
We have the nervous system—and you've either studied this already
or it's coming—where we have neurons that produce neurotransmitters
and cause a response in a target cell.
In the endocrine system,
we have secreting cells that produce molecules
that are carried by the blood to distant targets.
Cells that have receptors for these molecules will get
a response, and cells without receptors are oblivious to the signal.
Neurons play this game too, by the way,
and neurons can secrete molecules that go directly into
the blood endocrine style.
And same response, if the target cells have receptors for those molecules,
then you get a response, and cells that do not have receptors don't.
Now the question that I want to address in this video has to do with how
hormones do their thing. In a traditional anatomy approach,
you end up having to memorize all of this stuff, and it really is a nightmare.
I propose that a chemical classification is going to be
much easier when we start talking about the function of these things.
When you talk about chemical classifications,
there are only 3 categories that we have to worry about, and I don't know about you,
but 3 is a lot more manageable.
So we're going to talk about all 3 categories and answer these kinds of questions.
These are very typical questions that you're going to see on a lot of exams.
There is only 1 fundamental question that you need to
know the answer to when you are approaching things like this.
That big question is,
what kind of ligand is it?
Is it polar? That is,
does it fear lipids?
Or is it nonpolar?
Does it love lipids?
If you know the answer to that question,
you're going to be able to talk about how
the hormone moves through membranes and how it dissolves in the blood.
If the molecule is polar,
polar molecules don't pass through membranes easily,
but they dissolve in the blood because the blood is mostly water.
If the molecule is nonpolar,
nonpolar molecules love membranes because they are very lipophilic,
but they have a hard time dissolving in the blood.
Ladies and gentlemen, that is it.
If you know what kind of ligand it is in terms of polarity,
you're going to be able to very easily predict
all kinds of things about the hormones behavior.
Here's a simplified view.
We're going to look at polar and nonpolar ligands.
Then we're going to look at the 3 different categories of hormones,
which are just different examples of these 2.
We have the secretory cell on the left,
and you can store polar ligands in membrane-bound vesicles, no problem.
When it is time to release them, you get exocytosis.
Here we have the little polar ligand being exocytosed, and it
dissolves very easily in the blood and can be carried around the body.
However, when it comes time to effect a target cell,
because it's polar, it doesn't move through the target cell membrane,
it has to bind to a surface receptor, and you'll get a signal transduction mechanism,
and that is how the molecule exerts its effects.
On the other hand, if the ligand is nonpolar, then
a secreting cell can't store it in any membrane-bound vesicle.
They're just made as they're needed, and then
they diffuse through the membrane very easily.
The problem that nonpolar ligands have is that they don't move very easily in the blood.
They are going to require a carrier molecule.
We'll get to see what those look like.
They are so cool.
In terms of the target cell, because they're nonpolar,
they can diffuse right through the cell membrane and bind to
receptors either in the cytoplasm or in the nucleus.
You're going to get these questions.
For any given hormone that they're going to give you,
they're going to ask, how is it made and stored and released?
The answer depends on whether it's polar or not.
If it's polar, you can make those ligands in advance
and store them and release them by exocytosis.
If it's nonpolar,
you can't store them because they dissolve right through lipids.
They're made as needed, and they're released by diffusion.
Another question: how are they carried in the blood, and what's the half-life?
Again is it polar or not?
If it's polar, it's going to dissolve in blood plasma,
no problem, but it doesn't last very long.
It's going to have a short half-life.
If it's nonpolar, it requires transport molecules, and it will have a longer half-life.
It's almost like those transport molecules protect the ligand from degradation.
You're going to have to know how the hormone enters
target cells and where the receptors are.
Again, if it's polar,
then it can't enter the cell directly.
It's going to have to bind to a surface receptor.
If it's nonpolar, it enters the cell easily and will
bind to either cytosolic or nuclear receptors.
What's the cellular response and the lag time?
Again, is it polar or not?
If it's polar, usually the hormone will cause modifications of existing proteins.
Signal transduction mechanisms usually do that.
If it's nonpolar, usually you're going to look at induction of
new proteins in the target cell, and that takes a lot longer.
You're going to have a higher lag time.
Now we can look at all 3 classes of hormones and see what they do.
Peptide hormones are first.
There are a lot of peptide hormones,
so I just gave you a partial list so you can look through it
and see many of the hormones are probably familiar to you.
All of them work this way.
All peptide hormones are polar,
so they cannot pass through membranes.
They will require signal transduction,
but they dissolve very easily in the blood.
Hopefully now this makes some sense.
Peptide hormones are made in advance.
They're released by exocytosis.
They dissolve in the plasma.
They don't last very long,
and they require a cell surface receptor where they cause
signal transduction and the modification of existing proteins in the target cell.
How cool is that?
Let's look at steroid hormones next.
Steroid hormones are all made from cholesterol and they have a lot of roles in the body.
I'm showing a biosynthesis pathway just so you
can see some of the steroids and how they're interconverted one with another.
Steroid hormones are nonpolar,
so they pass very easily through membranes,
but they do not dissolve in the blood.
They're going to require carrier molecules.
Now, I want to show you some of
these carriers because they are really interesting, and I think
it'll give you a sense of how steroid hormones are in the body.
These protein carriers include SHBG.
These are sex hormone binding globulin,
and they are found, interestingly enough,
in all vertebrates other than birds.
That's interesting. We also have transcortin, which transports progesterone,
cortisol, and other corticosteroids, and
steroid hormones as a result of being in a sense protected by these molecules,
they have a very long half-life.
I want to take a minute and show you what some of
these molecules look like, because they are so cool. Let's take a look.
These images were generated by PDB,
that's the protein database, and I have the unique identifier at the bottom.
You can go and play with this yourself.
What you're looking at are the 2 subunits of SHBG.
What we're going to see—I'm going to stop rotating it—
Here in the white arrows you can see the estradiol.
The green arrows are pointing to calcium ions.
You can really see—there's the estradiol again in a different view—
I hope you can see how protected that steroid hormone is.
Let's look at just 1 subunit so you can see it a little bit better.
Here's the estradiol hidden inside. It really is like
a protective barrier that allows this thing to be dissolvable in blood plasma.
Let's rotate it a little bit.
Gosh, that's so cool.
Look how protected that thing is. Also neat that you can see
that calcium ion and how that affects the shape of the entire structure.
I think this is just amazing to really see how cool these things are.
There's the estradiol 1 more time and the calcium ion.
That is just so awesome.
Now when you see these little cartoons and you see
steroid hormones in the blood in these little boats,
now you have a sense of what it really looks like.
Now steroids can move right through the target cell membrane, and they
bind generally to receptors in the cytoplasm or in the nucleus.
Let's go ahead and fill out our table, and you can see that,
gosh, it's because they're nonpolar.
They're made when they're needed;
they are released by diffusion.
They need those carrier proteins to be transported in the blood.
They last a long time and they bind to receptors in the cytoplasm or in the nucleus,
where they usually induce synthesis of new proteins.
Finally, we have amine hormones.
Let's look at amines.
Now when you see the word amine,
it should make you think of amino acid;
that is exactly where they come from.
Tryptophan is the source of melatonin and serotonin.
Tyrosine is used to make the catecholamines and the thyroid hormones. Here's tryptophan.
Tryptophan is tweaked a little bit to make melatonin,
which makes you sleepy,
and serotonin, which makes you happy.
That's my personal favorite.
Here's some biosynthesis pathways just in case you are
curious and you want to see how similar some of these structures are.
Here's a little simplified view.
Tyrosine is converted to the catecholamines in neural tissue:
dopamine, epinephrine, and norepinephrine.
Now how these amines work is based on their polarity.
They're polar; they can't pass through membranes, but they dissolve easily in the blood.
Do you see the pattern here?
Yes. They're made in advance and stored.
They're released by exocytosis where they can dissolve very easily in the plasma.
They don't last very long,
and they require cell surface receptors and
signal transduction mechanisms to exert their effects.
The last group, these are also amines,
but thyroid hormones we treat separately because they are a little bit different.
T3 and T4, we're talking about molecules that mainly regulate metabolism.
They're synthesized like peptide hormones,
but they behave like steroids once they're released.
This is strange.
Tyrosine is converted to T4,
which is then converted to T3.
Now students always ask me about the T4 and T3.
The numbers are just—check it out—
the number of iodine atoms in the molecule.
See, the structures actually help you, just how many iodine atoms there are.
Now what's interesting about thyroid hormones is that they're made in
advance because the precursors are polar,
so they can be stored in vesicles.
But as they get a signal for release,
they're tweaked a little bit chemically, and then they become nonpolar.
Their release and transport half-life, etc.,
all of that is like a steroid.
That's what makes thyroid hormones a little bit bizarre.
But again, once you understand that
the reason is because they're made as polar molecules,
but they're released in a non-polar form,
gosh, it all makes sense.
Now we have the completed table,
and what you should be able to do now is
make a table like this for yourself and see if you
can fill it out on your own just knowing
which of the categories are polar and which are not.
That's the secret to understanding what the heck these hormones are doing.
As always, I hope that was helpful.
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