Endocrinology - Adrenals and their Hormones

Question 1

Where are the adrenal glands located?

Answer 1

Embedded on the superior pole of each of the two kidneys.

Question 2

What are the different parts of the adrenal gland?

Answer 2

1. Adrenal Medulla - the centre of the gland.

2. The outer part is the cortex and has 3 zones - zona glomerulosa, zona fasciculata, zona reticularis.

Question 3

What is the Adrenal medulla made of and what does it produce?

Answer 3

It is made of chromaffin cells and produces Catecholamines (Adrenaline, noradrenaline and dopamine).

Question 4

What does the cortex produce?

Answer 4

Corticosteroids (Aldosterone and Cortisol) + small amounts of sex steroids.

Question 5

Which part of the cortex does Aldosterone come from?

Answer 5

The zona glomerulosa.

Question 6

Which part of the cortex does Cortisol and sex steroids come from?

Answer 6

The two inner zones of the cortex (zona reticularis and zona fasciculata).

Question 7

Describe Cortisol synthesis

Answer 7

Cholesterol => Pregnenolone => 17-a-pregnenolone => 17-a-progesterone => 11-deoxycortisol => Cortisol

Question 8

Describe Aldosterone synthesis

Answer 8

Cholesterol => Pregnenolone => Progesterone => 11-deoxycorticosterone => corticosterone => Aldosterone

Question 9

What is the difference in the synthesis pathway between aldosterone and cortisol?

Answer 9

There is no P450cl in glomurelosa (aldosterone) but there is aldoesterone synthase.

Question 10

How is cortisol transported in the blood?

Answer 10

1. 80% bound to corticosteroid binding globulin (CBG).
2. 10% bound to albumin.
3. 10% free.
   Cortisol is much more selective to CBG.

Question 11

How is Aldosterone transported in the blood?

Answer 11

1. 40% free.
2. 15% bound to CBG.
3. 45% bound to albumin.
   Aldosterone is much less selective compared to cortisol, hence there is more free aldosterone.

Question 12

Is there a higher concentration of cortisol or aldosterone in the blood?

Answer 12

Cortisol, by a 1000 fold.

Question 13

Do cortisol levels change throughout the day?

Answer 13

Yes

Question 14

Do aldosterone levels change throughout the day?

Answer 14

no, your POSITION is more important as aldosterone in involved in control of fluid and balance.

Question 15

What are the actions of aldosterone? (2)

Answer 15

1. Stimulates Na+ reabsorption in the distal convoluted tubule and cortical collecting duct (important in kidneys and sweat glands).
2. Stimulates K+ and H+ secretion in the distal convoluted tubule and cortical collecting duct (important for pH regulation of the blood).

Question 16

What is the mechanism of action of aldosterone?

Answer 16

1. Diffuses into the cell and binds to intracellular receptors.
2. The complex formed moves into the nucleus and binds to DNA - acts as transcription factor.
3. Stimulates the synthesis of certain proteins for enzymes or pumps.
4. Also stimulates action of the Na+ ATPase pump on basolateral membrane.
5. Stimulates Na+ ion channels on apical membrane.

Question 17

How does aldosterone stimulate the release of vasopressin?

Answer 17

Aldosterone stimulates the reabsorption of Na+ into the blood. This increases the osmolality of the blood. Increased osmolality of the blood stimulates the release of vasopressin.

Question 18

What is a long term problem you get if you maintain a high extracellular fluid volume?

Answer 18

Hypertension.

Question 19

What is the name given to the cells that line the afferent arteriole into the kidneys that are next to the glomerulus?

Answer 19

The Juxta-glomerular cells.

Question 20

What is the name given to the specialized cells that line the ascending limb of the loop of Henle? And what do they respond to?

Answer 20

Macula Densa. Changes in Na+ concentration.

Question 21

What is the enzyme important for the production of aldosterone? And cells produce this enzyme?

Answer 21

Renin. Produced by the juxta-glomerular cells.

Question 22

What are the causes of Renin release? (3)

Answer 22

1. Decreased renal perfusion pressure.
2. Decreased Na+ load to the top of the loop of Henle.
3. Increased renal sympathetic activity.

Question 23

How does Renin stimulate the production of aldosterone?

Answer 23

1. Angiotensinogen (large protein) is released by the liver.
2. Renin breaks down angiotensinogen into angiotensin I.
3. ACE converts angiotensin I into angiotensin II.
4. Angiotensin II stimulates aldosterone production in the zona glomerulus.

Question 24

What are the other effects of angiosten

Answer 24

Vasoconstriction.

Question 25

What are other factors that affect aldosterone? (3)

Answer 25

1. Corticotrophin - enhances renin-angiotensin system.
2. Low Na+ concentration in the blood (increased reabsorption of Na+).
3. High K+ concentration in the blood (increased secretion of K+).

Question 26

What are the metabolic effects of cortisol?

Answer 26

OVERALL EFFECT TO INCREASE BLOOD GLUCOSE CONCENTRATION.

1. Stimulates peripheral protein catabolism.
2. Hepatic gluconeogenesis.
3. Lipid metabolism.
4. Enhances effects of glucagon and catecholamines.
5. Stimulates glycogenolysis.
6. Makes tissues less responsive to insulin.

Question 27

What is the syndrome as a result of excessive cortisol production?

Answer 27

Cushing’s syndrome - arms and legs really thin because of the loss of muscle.

Question 28

How does cortisol affect memory?

Answer 28

1. Serotonin promotes granule cell division (used to make memories).
2. Cortisol enhances the sensitivity of serotonin receptors in the hippocampus.

Question 29

What are the effects of supra-physiological amounts of cortisol?

Answer 29

1. Anti-inflammatory action.
2. Immunosuppressive action.
3. Anti-allergic action.

Question 30

Which receptor does aldosterone bind to?

Answer 30

Almost entirely to the mineralcorticoid receptor (MR).

Question 31

Which 2 receptors does cortisol bind to?

Answer 31

Binds equally to both the mineralcorticoid and the glucocorticoid receptor.

Question 32

Why doesn’t cortisol constantly bind to the aldosterone receptors even though it has a concentration 1000 times greater than aldosterone?

Answer 32

Because the kidneys produce an enzyme, called 11-beta-HSD II, which converts cortisol into an inactive form cortisone. This prevents cortisol interfering with aldosterone receptors.

Question 33

Explain the mechanism of cortisol

Answer 33

Cortisol binds to intracellular receptors and has a genomic effect. Example is one protein produced called annexin 1.

1. Annexin 1 has an autocrine effect on cell.
2. The binding has effect on phospholipase enzyme, which works on phospholipids in the membrane to produce arachidonic acid that is a precurser to prostaglandins.
3. Therefore cortisol blocks the production of prostaglandins.

Question 34

How is cortisol levels controlled?

Answer 34

1. Corticotrophin controlled by hypothalamic hormones.
2. Cortisol has negative feedback - direct (pituitary) and indirect (hypothalamus).
3. ACTH has negative feedback on hypothalamus.
4. There is a circadian rhythm for cortisol which originates from biological cock, which resides in the suprachiasmatic nucleus.

Question 35

How should blood sampling be arranged for cortisol?

Answer 35

Cortisol levels vary with time and therefore blood sampling should be done when cortisol levels are expected to be at its highest or lowest.

Question 36

What is the androgen produced by the adrenal glands?

Answer 36

DHEA. It is a very weak androgen and is a precursor for oestrogen. Important to post-menopausal women as a precursor for oestrogen in the absence of ovarian steroids.