Adrenals and corticosteroids

Question 1

Where are corticosteroids produced?

Answer 1

cortex
different zones produce different corticosteroids
they drain through medulla and leave via central vein

Question 2

What cells are found in the medulla?

Answer 2

chromaffin cells
adrenaline (80%)
NA (20%)
some dopamine

Question 3

What does zona glomerulosa importantly have?

Answer 3

aldosterone synthase

convert corticosterone to aldosterone

Question 4

Why are only few sex steroids produced?

Answer 4

require extra enzymes

in zona fasciculata and reticularis these enzymes are present at very low []

Question 5

Describe the binding of corticosteroids from the adrenal glands?

Answer 5

most cortisol is 90% protein bound/unactive, 40% aldosterone bioactive/unbound

Question 6

What is the effect of 5% cortisol/aldosterone displacement from binding proteins?

Answer 6

it would cause a greater increase in glucocorticoid receptor binding than for mineralocorticoid (50% increase in free cortisol)

heavily plasma protein bound substances are affected to a greater extent by small protein bound changes

Question 7

What receptors does cortisol bind to?

Answer 7

MR and GR receptors (equally)

aldosterone can only bind to MR

Question 8

How does aldosterone have an effect is cortisol is 1000x higher [] in blood?

Answer 8

some tissues contain 11bHSD2 (hydroxysteroid dehydrogenase 2) that metabolises cortisol into inactive form (cortisol will have no effect)

therefore aldosterone need to bind to MR to take effect
high expression:
- in the kidney
- placenta (stop maternal cortisol getting to foetus - may inhibit growth)

Question 9

Describe the locations and actions of the RAAS?

Answer 9

renin from kidney juxtaglomerular cells acts on angiotensinogen from liver –> angiotensin I

ACE in lungs acts on this to make angiotensin II

angiotensin II is the effector hormone, enters zona glomerulosa of adrenal cortex and stimulated aldosterone production

Question 10

What are the 3 stimuli of zona glomerulosa aldosterone production?

Answer 10

angiotensin II
HIGH K
LOW Na

Question 11

What are the optimal conditions for normal physiology?

Answer 11

cortisol heavily bind MR receptor, partially bind GR receptor

in stress: maximal GR and then return to normal

Question 12

What are the effects of cortisol in normal . physiology?

Answer 12

• cortisol ensures high glucose, high glucose stores
• increase gluconeogenesis in liver
• increases glucokinase (storage of glucose as glycogen)
• stops glucose storage peripherally (not accessible)
• decrease blood flow to skeletal muscle/adipose tissue, decrease GLUT4 (cannot transport glucose to SM), decrease lipoprotein lipase (stop storage of FA in adipose tissues)
• pro memory: upregulates serotonin 5HT 1A receptors, serotonin innervation promotes granule cell formation

Question 13

Where are new memories made, stored and produced?

Answer 13

DANTATE GYRUS
in hippocampus
cortisol increases capacity to respond to serotonin

Question 14

What are the effects of cortisol supra-physiologically?

Answer 14

• anti inflammatory/ immunosuppressive

can increase susceptibility to disease

Question 15

What enhances effect of cortisol?

Answer 15

caffeine

alcohol

Question 16

Pathological effects of cortisol?

Answer 16

high cortisol
high GR and MR binding
excessive long term GR activation - cortisol has a negative effect on serotonin
hippocampus shrinks 
decrease ability for LT memory formation

Question 17

Describe the production of adrenal androgens

Answer 17

made in zona reticularis
(androstenedione, DHEA - dehydroepiandrostenedione)
converted into active androgens (testosterone in peripheral tissues)

women - adrenal production of DHEA, DHEAS increases androgen production substantially

men - androgen production of adrenals small