Lecture 24: Adrenal Steroids Flashcards Preview

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Flashcards in Lecture 24: Adrenal Steroids Deck (100)
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1

Describe the naming nomenclature of adrenal steroids.

Number of Cs:
- 21 Cs: pregn-
- 19 Cs: androst-
- 18 Cs: estr-

Ring double bonds:
- None: -ane
- One: -ene
- Two: -diene

2

What are the first 3 steps common to the synthesis of all adrenal steroids? What is the rate-limiting step? What are all 3 enzymes activated by?

1. Esterase: lipid droplets made of cholesterol ester => free cholesterol + FA
2. StAR protein: cytosol free cholesterol => mito cholesterol (rate-limiting step)
3. P450 side-chain cleavage (P450-SCC): cholesterol => pregnenolone (cut off 6Cs with carboxyl group left on C20) + isocaproaldehyde

All 3 activated by cAMP

3

How many Cs in pregnenolone?

21 Cs

4

How many Cs in isocaproaldehyde?

6 Cs

5

Describe the detailed cell composition of the adrenal cortex with the function of each layer.

1. Connective tissue capsule
2. Zona glomerulosa: where mineralcorticoids are synthesized (aldosterone mostly)
3. Zona fasciculata: where glucocorticoids are synthesized (cortisol mostly)
4. Zona reticularis: where androgens are synthesized
5. Medulla: where catecholamines are synthesized (DHEA mostly)

6

What is another name for 11-deoxycorticosterone?

21-hydroxyprogesterone

7

Where is the enzyme 18-hydroxylase found?

Zona glomerulosa of the adrenal cortex

8

Explain how the RAA system works to stimulate aldosterone secretion. 6 steps

1. Drop in blood pressure/volume/sodium OR increase in potassium OR edema OR renal nerve activation
2. Juxtaglomerular apparatus (JGA) in kidney releases renin into circulation
3. Renin converts angiotensinogen secreted by the liver to angiotensin I
4. Angiotensin-converting enzyme (ACE) in vascular endothelium (secreted by the lungs) converts angiotensin I to angiontensin II and III
5. Angiotensin II/III bind to receptors on cells in the ZG of adrenal cortex to stimulate aldosterone production
6. Aldosterone acts on kidney tubules to stimulate sodium reabsorption to raise BP and potassium excretion to inhibit stimulation of aldosterone

9

What are the 2 regulators of aldosterone synthesis? Which is the main one?

1. RAA system (main one)
2. K+ levels

10

What 2 steps of aldosterone synthesis does angiotensin II stimulate?

1. Cholesterol to pregnenolone
2. Corticosterone to aldosterone

11

What 2 steps of aldosterone synthesis does K+ stimulate?

1. Cholesterol to pregnenolone
2. Corticosterone to aldosterone

12

What other effects does angiotensin II have other than stimulating aldosterone synthesis?

Increases blood pressure through vasoconstriction and increases ADH secretion

13

What are hypertensive patients prescribed? Example?

ACE inhibitors
Eg: ramipril (altace)

14

Where do the juxtaglomerular cells sense BP?

The renal artery

15

What 2 forms does aldosterone exist in?

1. Aldehyde
2. Hemiacetal

16

How is aldosterone prevented from working on glucocorticoid receptors? What else is this super important for?

Its hemiacetal form protects the C11 hydroxyl
This is very important because steroids that do not have a protected C11 hydroxyl group (aka glucocorticoids) are deactivated by conversion of the hydroxyl into a ketone

17

Can the zona glomerulosa make steroids of the cortisol, androgen, or estrogen pathways? Why/Why not?

NOPE because it lacks the enzyme 17-α-hydroxylase

18

What 2 carrier proteins bind aldosterone in blood? Describe the binding.

1. Albumin
2. CBG

Both weakly bound to aldosterone

19

What is the half life of aldosterone?

15 min

20

What other molecule on the aldosterone pathway has mineralcorticoid activity?

11-deoxycorticosterone

21

What step of the RAA system is the controlling step?

Renin production

22

How is angiotensinogen II (and III) inactivated?

Angiotensinases

23

What is the main glucocorticoid in rodents?

Corticosterone

24

Describe the regulation of cortisol secretion.

- Hypo: CRH
- Ant. Pit: CRH: POMC => ACTH
- Adrenal cortex: ACTH: + cortisol + aldosterone

Cortisol exerts (-) feedback on both the hypo and ant. pit.

25

What 2 carrier proteins bind cortisol in blood? Describe the binding.

1. CBG: strong
2. Albumin: weak

26

What is the half-life of cortisol?

1.5-2 hrs

27

How much aldosterone is free in the blood? Why?

36%
To be able to quickly respond to changes in BP

28

How much cortisol is free in the blood? Why?

8%
So it has a longer half-life and can regulate blood glucose levels over a longer period of time (hours between meals)

29

What carrier protein binds corticosterone in the blood?

CBG

30

What is the half-life of corticosterone?

Less than 1 hour