This content explains the physiological pathway of cortisol production, its molecular mechanisms of action, and its diverse effects on the body, particularly in response to stress and low blood glucose.
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All right, ninja nerds. In this video,
we're going to continue our discussion
about the adrenal gland. If you guys
haven't already, go and watch the video
on the adrenal gland where we talk about
the zona glomemeillosa. Okay, in this
video, we're going to focus on the
zonaficulata. Okay, so zonapiculata is
again this middle layer of the adrenal
cortex because there's three layers of
the adrenal cortex, right? This orange
layer was the zona glomemeilosa. We
talked about that one. This green one is
the zona faciciculata. Okay. So what's
this layer here called? This green
layer. It's called the zona
faciciculata. Okay. Zona faciciculata.
It's this middle layer here and it's
responsible for secretreting a specific
hormone that we put in a category of
glucocorticoid. So cortisol is the
specific one. And then the other part of
the adrenal cortex is this uh purple
layer which is the zona reticularis. And
we'll talk about that one next. Okay. So
zonop faciciculata where does all of
this response for this guy to make this
hormone start? It starts in the
hypothalamus. So in the hypothalamus you
have these specific nuclei. You see
these these red nuclei up here in the
hypothalamus. These red nuclei are
called the parah
ventricular nucleus.
And these nuclei are responsible in the
hypothalamus for secretreting a specific
type of hormone. This hormone that they
release is called corticotropen
releasing hormone. So CR again it's
called corticotropen releasing hormone.
That corticotropen releasing hormone
comes down through the hypothesial
portal system and stimulates the
corticotropes that are present within
the anterior pituitary gland. When these
corticotropes are stimulated by
corticotropen releasing hormone, they
secrete into the blood
blood
adrenal corticoot tropic hormone. Okay.
So again, what is this hormone here
called? It's called
adreno corticotropic hormone. Once this
adreninocorticotropic hormone is
released from the anterior pituitary by
the stimulus of corticotropen releasing
hormone, act then moves and goes to
stimulate the
zonopiculata. So what we're doing here
is we're blowing up a cell of the
zonopiculata. We're taking a very deep
look at the molecular mechanisms
involved. So let's follow this
adreninocorticotropic hormone over here.
So look what the adrenal corticotropic
hormone does. It comes over here and it
binds onto this G-proin coupled
receptor. See this orange protein here?
That's a G-proin coupled receptor. It's
a part of the cell membrane. So when
adrenal corticotropic hormone binds onto
this receptor, it activates you guys
should already know this by heart.
Now a G stimulatory protein. Normally
Gstimulatory proteins is bound to GDP
which keeps it off. But whenever ACT
binds, it takes and binds GTP to the G
stimulatory protein and then GTP turns
the G- protein on. Once this G- protein
is on, it's activated and it's moves
along the actual cell membrane. When it
moves along the cell membrane, you guys
know that there's an aector enzyme
that's a part of the cell membrane. Look
at this guy. This guy right here is called
called
adenolate cylace, right? And what does
this guy do once it receives the
stimulus from this G stimulatory
protein? He then takes
ATP and converts it into cyclic AM. And
then look what cyclic AMP does. It
activates a special enzyme. And this
enzyme is called protein kynise A. And
you know that kynases are responsible
for phosphorolating different types of
proteins. Proteins and what? Okay. So
you guys have already known that we've
already gone through transcription and
translation where we take DNA to make
mRNA mRNA to make proteins. But those
are for protein hormones. You know in
this cell we're making steroid hormones.
Steroid hormones don't come from DNA or
from mRNA. They come from a basic unit
called cholesterol. So what is that
molecule called? It's called
cholesterol. So cholesterol is the basic
unit for this synthesis of steroid
hormone. Not DNA, not mRNA, not
proteins. We're making steroid hormones.
So what happens is cholesterol actually
pregnnolone. And then pregnnenolone
actually gets converted into what's called
progesterone. And then progesterone
actually gets converted into what's
hydroxy
progesterone and then into 11
11
deoxy cortisol and then look into
into
cortisol. This is the one that we care
about. We care about cortisol. The whole
point of me going through this pathway
was to show you that before we were
taking DNA, converting it into mRNA, and
then translating it to make proteins at
the ribosomes. Now, we're starting with
a different thing. We're starting with
cholesterol and using all these
different types of uh intermediates to
get to cortisol. Cholesterol is the
starting point. Now, now, out of all the
enzymes that control all of these steps,
one of the more important enzymes is
right here. And I'm just going to put it
down because we're going to talk about
it later. And this one's called 21
21
hydroxilase, okay? Called 21 hydroxilase
enzyme. And he catalyzes this step, the
conversion of 17 hydroxy progesterone
into 11
deoxycortisol. Now, where is this
protein kynise A going to be involved in
here? He's actually helping to stimulate
a lot of these enzymes. So, you know how
21 hydroxilates is acting in this step?
Well, there's multiple enzymes. There's
enzymes working in this reaction,
enzymes working in this reaction,
enzymes working in this reaction, and
even enzymes working in this
reaction. Protein kynise A is
phosphorolating different types of
enzymes involved within this enzyatic
reaction to produce cortisol. Okay. So
now if protein kynas is phosphorolating
a lot of these enzymes involved in this
pathway, it's going to help to lead to
the synthesis or the formation of
cortisol. So that's why
adreninocorticotropic hormone is one of
the strong stimuli for cortisol
synthesis. Why? Because it stimulates
this intracellular pathway to make pKa
protein kynise A which phospholates
enzymes for the synthesis of cortisol.
So now we've made cortisol. What is
cortisol going to do? He's going to get
pushed out into the blood. But you know
cortisol, he's special. Cortisol is
special because he can't be in the blood
in free form. He's a lipid soluble
hormone or a steroid hormone, right? So,
he's not water soluble. He has to be
bound to certain types of transport
proteins. So, there's two transport
proteins. Let's say I bifurcate it here
and I bifurcate it here. And here's our
cortisol. This little purple dot here.
He's going to bind on to two different
types of transport proteins. Let's say
that we use one as an orange. One's an
orange transport protein, right? Look at
this guy. about
25% of the
actual steroid on this cortisol is
actually bound to this one. So about
25%. This one is called that orange
protein is called
albumin. Okay. The other 75% of it is
bound onto this nice little blue transport
protein. about 75% of
it. And this protein right here is
called cortico
steroid binding globbulin. Okay. Another
name for it is actually called
called
transcortin. Okay. So that transcortin
or corticosteroid binding globulin is
actually carrying and transporting most
of the cortisol. Okay. Now cortisol gets
transported to multiple different target
organs through the blood. What are some
of these target organs? Let's start with
the muscles. So let's say cortisol comes out
out
here. When cortisol comes over to the
muscles, so let's say cortisol comes out
here and he acts on the muscles. You
know inside of our muscles we have
proteins, a lot of proteins that make up
a lot of different types of myofilaments
or other different components. So let's
say here I I
represent these proteins here as like
this squiggly like structure, right? And
these little red dots that I have on it
are amino acids because amino acids are
the building blocks of proteins, right?
And how do you identify proteins? One
has a aminois and the other one has a
caroxy terminus, right? So there's our
protein. Look what cortisol does. Now
cortisol is a steroid hormone. So the
only way he can work is he has to come
into this cell and let's say here's your
DNA. He has to activate specific types
of intracellular receptors, right? So
what he'll do is he'll stimulate, right?
because he can actually move through the
cell. He can move to the cell, bind onto
an intracellular receptor and activate a
specific gene. That gene will make mRNA.
It'll get transcribed, right? And then
it'll get translated to make proteins.
Look what these proteins are going to
this. Look as this little scissor
enzymes. These enzymes are going to
start cutting up the proteins. They're
proteases. Proteases break the peptide
bonds. And look what you release out of
this reaction. out of this reaction.
Look what look what gets released into
the bloodstream as a result. All these
different amino acids. So all these
amino acids, those little
circles are released into the
bloodstream. So what are these things
here called? These are called amino
acids. Okay? So these amino acids are
the building blocks of this whole thing
which is called proteins. Right? So we
have proteins here that are getting
broken down, catabolized into amino
acids. So what's it doing in this area
right here? What's it stimulating? It's stimulating
