Cortisol and Aldosterone Synthesis – Adrenal Cortex

by Carlo Raj, MD

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    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.

    About the Lecture

    The lecture Cortisol and Aldosterone Synthesis – Adrenal Cortex by Carlo Raj, MD is from the course Adrenal Gland Disorders.

    Included Quiz Questions

    1. Cholesterol to pregnenolone
    2. LDL to cholesterol
    3. Pregnenolone to cortisol
    4. LDL to pregnenolone
    5. Cholesterol to cortisol
    1. LDL will not be endocytosed into the cell.
    2. ACTH will not bind to the receptor.
    3. Cholesterol will not be released from LDL.
    4. Desmolase will not be formed.
    5. Pregnenolone will not be formed.
    1. It is stimulated by sodium ions.
    2. It is present only in the glomerulosa cells.
    3. It is stimulated by angiotensin II.
    4. It converts corticosterone to aldosterone.
    5. It is a necessary enzyme for the formation of aldosterone.
    1. More pregnenolone is synthesized from cholesterol.
    2. Less angiotensin II is formed.
    3. There is less formation of aldosterone from corticosterone.
    4. There is a negative effect on the IP3 mechanism.
    5. Less cholesterol is released from LDL.

    Author of lecture Cortisol and Aldosterone Synthesis – Adrenal Cortex

     Carlo Raj, MD

    Carlo Raj, MD

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