>> 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.
It makes a big difference on my end.
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.
And 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-dependence signals and paracrine
and autocrine secretions.
For long-distance communication, we've got a couple 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, and 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 kind of 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.
And when you talk about chemical classifications,
there are only three categories that we have to worry about.
Now I don't know about you, but three is a lot more manageable.
So we're going to talk about all three 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 one fundamental question that you need
to know the answer to when you are approaching things
like this.
And that big question is, what kind of ligand and 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.
So 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,
very lipophilic, but they have a hard time dissolving
in the blood.
And 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.
So here's a simplified view.
We're going to look at polar and nonpolar ligands,
and then we're going to look at the three different categories
of hormones, which are just different examples of these two.
So 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.
And here, we have a little polar ligand being exocytosed,
and it dissolves very, very easily in the blood
and can be carried around the body; however,
when it comes time to affect 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 kind
of membrane-bound vesicle.
So 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.
And 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.
So you're going to get these kinds of 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.
And 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.
You can't store them because they dissolve right
through lipids.
So 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.
So you're going to have a higher lag time.
Now we can look at all three classes
of hormones and see what they do.
Peptide hormones are first.
There are a lot of peptide hormones.
So I just give 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.
And 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.
And I'm showing a biosynthesis pathway just so you can see some
of the steroids and how they're inter-converted 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 sort of are in the body.
These protein carriers include SHBG.
These are sex hormone-binding globulins, 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.
And I want to take a minute and show you what some
of these molecules look like because they are so cool.
So let's take a look.
All right.
These images were generated by PDB.
That's the protein database,
and I have the unique identifier at the bottom.
So you can go and play with this yourself.
So what you're looking at are the two subunits of SHBG.
And what we're going to see, I'm going to stop rotating it,
and here, with the white arrows, you can see the estradiol.
The green arrows are pointing to calcium ions.
And you can really see there's the estradiol again
in a different view.
And I hope you can see how protected
that steroid hormone is.
Let's look at just one subunit
so you can see it a little bit better.
So here's the estradiol kind of 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 one more time and the calcium ion.
Okay, that is just so awesome.
So 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.
So 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,
and tyrosine is used to make the catecholamines
and the thyroid hormones.
So 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.
So 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.
The thyroid hormones we treat separately
because they are a little bit different.
So 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.
So this is kind of 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.
So their release and transport, half-life, et cetera,
all of that is like a steroid.
So 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 nonpolar form, gosh, it all makes sense.
So 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.
And that's the secret
to understanding what the heck these hormones are doing.
As always, I hope that was helpful.
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