Corticosteroids

Question 1

Corticosteroids derive from which organic molecule?

Answer 1

Cholesterol

Question 2

What can steroid hormones form

Answer 2

Sex hormones

Corticosteroid hormones

Question 3

What are the two types of corticosteroid hormones?

Answer 3

Glucocorticoids and mineralcorticoids

Question 4

What do glucocorticoids do and give an example

Answer 4

They have a role in regulation of glucose metabolism and synthesis.

Cortisol:
Decrease carbohydrate uptake and ultilisation
Increased protein metabolism
Regulatory effects on host defence mechanisms

Question 5

What do mineralcorticoids do and give an example

Answer 5

They link to water and salt balances

Aldosterone:
Regulate water and electrolyte balance

Question 6

Where are BOTH glucocorticoids and mineralocorticoids produced?

Answer 6

Adrenal glands

Question 7

Where are mineralocorticoids synthesised?

Answer 7

Zona glomerulosa (outermost layer on adrenal cortex)

Question 8

Where are glucocorticoids synthesised?

Answer 8

Zona fasciculata (middle layer on adrenal cortex)

Question 9

How are corticosteroids regulated?

Answer 9

They are under the control of the hypothalamic-pituitary- adrenal (HPA) axis

Question 10

What is Cushing’s syndrome and what are the symptoms for it?

Answer 10

When there is overactivity and exposure to excessive levels of endogenous glucocorticoids

The symptoms are:
Hypertension
Easy bruising 
Increased abdominal fat 
Thinning of skin and thin arms and legs
Osteoporosis 
Avascular necrosis of femur

Question 11

What is Addison’s disease?

Answer 11

When there is adrenal insufficiency

Question 12

How does dimerisation of the receptors lead to the inhibition of transcription?

Answer 12

After the dimerisation of the receptors, they bind to the recognition site on DNA
The dimerisation of the receptors binds to the nGRE, repressing the activity of transcription factors which inhibits transcription

Question 13

Glucocorticoids can also silence proinflammatory genes. What is this called?

Answer 13

Gene transrepression

Question 14

How do glucocorticoids silence proinflammatory genes?

Answer 14

The receptors bind to the TFs Fos and Jun which inhibit transcription of AP-1.
This means there is less response to cytokines, growth factors, stress and bacterial and viral infections

Question 15

Which specific pathway silences proinflammatory genes?

Answer 15

The NKkB pathway

Question 16

Where are glucocorticoids absorbed and metabolised?

Answer 16

They are readily absorbed in the gut

They are extensively metabolised in the gut wall and liver

Question 17

How do hydrocortisones bind in the blood?

Answer 17

Hydrocortisone binds to:

• corticosteroid binding globulin (transcortin)
• albumin in the blood

Question 18

What are the pharmacokinetics of synthetic glucocorticoids?

Answer 18

Only bind to albumin and are more slowly metabolised in the liver

Question 19

How are glucocorticoids usually administered?

Answer 19

Usually tropical to deliver high concentration

Question 20

What are the side effects of glucocorticoid therapy?

Answer 20

Suppression of the response to infection or injury
Cushing’s syndrome
Osteoporosis
Hyperglycaemia
Muscle wasting
CNS effects such euphoria and psychosis, depression