Glucocorticoids and Mineralocorticoids

Question 1

What is the difference between cortisol and cortisone?

Answer 1

they are glucocorticoids and cortisone is the less active metabolite of cortisol
- it can be converted back to cortisol

cortisone and cortisol have the same structure except cortisol has a hydroxyl group whereas cortisone has a ketone group

Question 2

What is role of glucocorticoids in metabolism?

Answer 2

increases glucose biosynthesis and glucose release from glycogen in the liver

increases protein catabolism and protein synthesis

decreases osteoblast formation/activity
- increases risk of osteoporosis

decreases calcium absorption from the GI tract

decreases thyroid stimulating hormone secretion

Question 3

What is the role of glucocorticoids in anti-inflammation?

Answer 3

decreases synthesis of
- prostaglandins, cytokines and interleukins

decreases proliferation and migration of
- lymphocytes and macrophages

Question 4

What are the structural features that affect activity of dexamethasone and betamethasone (glucocortcoids)?

Answer 4

hydroxyl (OH) at C11 is essential for activity

alpha fluorine (F) at C9 increases activity

double bond between C1 and C2 increases glucocorticoid activity over mineralocorticoids
- introduces selectivity

methyl (CH3) at C16 reduces mineralocorticoid activity
- does not affect glucocorticoid activity

Question 5

What are the long term side effects of steroids?

Answer 5

osteoporosis
adrenal suppression
ulcers
fluid retention
increased risk of infection

Question 6

How is cortisol synthesised from 17 alpha hydroxyprogesterone?

Answer 6

addition of 2 OH (hydroxyl)
- on the side chain
- on C11

Question 7

How does the adrenal axis produce cortisol?

Answer 7

anterior pituitary corticotroph cells synthesise pro-opiomelanocortin (POMC)

POMC is cleaved to give
- adrenocorticotrophic hormone (ACTH) = stimulates cortisol production
- beta endorphin = an endogenous opioid
- melanocyte stimulating hormone (MSH) = confers skin pigmentation

Question 8

How is ACTH released? How does it stimulate cortisol release?

Answer 8

ACTH is released according to circadian rhythm
- greatest size and frequency in the morning

ACTH binding to receptor in the cytoplasm of cells in the adrenal cortex causes delivery of cholesterol from cellular stores to inner mitochondrial membrane
- initiates cortisol production from cholesterol
= is the rate limiting step

Question 9

What are the types of glucocorticoid receptors?

Answer 9

Type 1 - associated with mineralocorticoids

Type 2

both have similar affinities for glucocorticoids

Question 10

How is aldosterone synthesised from progesterone?

Answer 10

addition of
- one hydroxyl (OH)
- a ketone

Question 11

How do aldosterone and cortisol both bind to type 1 glucocorticoid receptors? How is aldosterone activity ensured to dominate over cortisol?

Answer 11

they bind to type 1 receptors with the same affinity
- but binding of each leads to binding of the receptor dimer to different response elements resulting in stimulation of different genes

to ensure aldosterone activity dominates over cortisol, in mineralocorticoid responsive tissues there is a high concentration of 11 beta hydroxysteroid dehydrogenase
- converts cortisol to cortisone which is inactive