00:01
Here, we’ll go into a little bit more detail
with cortisol and aldosterone synthesis, we’ll
begin with cortisol synthesis.
00:08
Here we have cortisol synthesis.
00:10
Cortisol synthesis, you should be jumping
directly into the middle layer which is the
fasciculata.
00:16
Here, we have a fasciculata cell, the adrenal
cortex and I want you to begin on the left,
you’ll notice that we have ATP being converted
into cyclic AMP.
00:25
So, therefore, this is ACTH binding to a receptor
converting ATP into cyclic AMP.
00:30
Cyclic AMP has a number of pathways that it’s
going to then follow; the pathway here for
cyclic AMP responsible for your LDL.
00:38
Remember, what are we trying to form here?
We’re trying to form cortisol and anytime
you form cortisol, you must begin with cholesterol,
right?
How do you bring in cholesterol into the cell?
LDL receptors.
00:50
So, here’s LDL receptors with the help of
cyclic AMP allows you to then endocytosis.
00:56
Your LDL and cholesterol and then you begin
the process.
01:01
Your cholesterol will be converted into pregnenolone
and that is your rate limiting enzyme and
what is that please?
Desmolase.
01:09
So, if you want, make sure you go back and
take a look and then with the middle layer,
remember it’s 17 hydroxy.
01:15
Alright, so, 17 hydroxypregnenolone, 17 hydroxyprogesterone,
so on and so forth and ultimately, all of
these cortisols are being secreted into your
blood and that’s what you’re seeing on
the-on the right there and your-your cortisol
will then go to the respective organ maybe
the liver and such.
01:34
And then with the help of glucagon may then
begin the process of gluconeogenesis.
01:39
Cortisol synthesis, number one, ACTH bind
to receptor cyclic AMP.
01:44
Cyclic AMP allows for LDL to come into the
cell.
01:48
This LDL then delivers the cholesterol, it’s
necessary for your cortisol synthesis one,
two and three in the picture and explanation.
01:58
Number four, what we have here is conversion
and with cholesterol.
02:05
Number five, we have desmolase which allows
you to then form your 17 hydroxypregnenolone/progesterone.
02:11
Remember the next enzyme?
You should be quite familiar with it now and
the next enzyme after… well, at first, you
have 3 beta hydroxysteroid dehydrogenase.
02:23
The next enzyme after that will be 21 beta
hydroxylase, next enzyme after that will be
11.
02:30
If you want to go from 21 to 11 in chronological
order, if that helps you.
02:36
And all of this is then going to help you
form your cortisol.
02:38
Number six, the cortisol will come out through
your membrane into circulation.
02:45
Remember though, you have to have… remember,
cortisol’s lipid soluble.
02:48
So, therefore, cortisol has to have a chaperone.
02:51
Hence, you see the green… the green dot
represents your cortisol, it’s bound to
a receptor known as cortisol-binding protein
or cortisol-binding globulin.
03:03
Where is it coming from?
It’s coming from the liver.
03:06
That discussion we’ve had in previous topics.
03:10
Let’s move on to the aldosterone synthesis.
03:15
The beginning stages of this will be relatively
similar to cortisol.
03:18
I need you to jump directly into the glomerulosa
which is superficial most layer, that’s
the cell that we’re dealing with.
03:25
The acronym sometimes that you can use for
adrenal cortex G, F and R… glomerulosa.
03:30
Here, also, we begin with the steps.
03:36
Now, the way that you will be producing your
aldosterone would be through aldosterone synthase;
this time I need you to begin on the right.
03:45
And on the right, ACTH could help, but you
also have the IP3 mechanism.
03:50
You have LDL, in the meantime, coming in,
allowing the cholesterol to come in, same
exact trigger that we saw earlier and this
time though, what is it that converts your
corticosterone into aldosterone?
That will be your aldosterone synthase and
that is stimulated by whom? Angiotensin II.
04:09
So, that’s the biggest difference here,
isn’t it?
And you should automatically be thinking about
the RAS system.
04:14
Could ACTH play a role?
Yes, it does, it’s a minor influence of
feedback.
04:18
However, the most important feedback mechanism
clinically you’re paying attention to is
RAS, RAS, RAS.
04:26
Do not forget about DUC that we talked about.
04:29
Number one, conversion of corticosterone into
aldosterone requires an enzyme, this is called
aldosterone synthase.
04:35
The name of the hormone responsible for converting
this or enzyme if you have… have you is
angiotensin II… number one.
04:42
Number two, formation of pregnenolone from
cholesterol is enhanced by angiotensin II
as well and also increase serum potassium
ion concentration helps you do that as well.
04:51
Remember, that potassium normally wishes to
efflux, however there are mechanisms that,
at this point, beyond the scope for your boards,
but the potassium will also allow you to convert
or begin or continue the process of aldosterone
synthesis.