Steroids

Question 1

What is the difference between cortisol and prednisone?

Answer 1

• prednisone has much more corticosteroid

- prednisone = extra O bond in the A ring and O group instead of OH group in C ring

Question 2

What are the 3 stages of stress?

Answer 2

1. alarm: acute stress (6-48 hours)
   - rapid decline in thymus, spleen, lymph glands
   - disappearance of fat and loss of muscle
2. resistance: chronic stress (2 days - 1 month)
   - adrenal glands are larger
3. exhaustion: pathogenic stress (>3 months)

Question 3

What happens when cortisol exceeds its normal range?

Answer 3

suppression of the immune responses

Question 4

What are unwanted effects of systemic glucocorticoids?

Answer 4

• oedema
• weight gain
• glycosuria
• osteoporosis
• hypertension
• glaucoma
• juvenile growth retardation
• hyperlipidaemia
• GI bleeding
• increased risk of infection
• HPA axis suppression

Question 5

What is the result of cortisol overproduction?

Answer 5

Cushing syndrome
peptic ulcer
glaucoma 
osteoporosis
avascular necrosis

Question 6

Why can chronic use of corticosteroids cause osteoporosis?

Answer 6

corticosteroids suppresses osteoclast functions and osteoblast function, but osteoblast function is suppressed much more

Question 7

What is the effect of glucocorticoids on carbohydrate metabolism?

Answer 7

hyperglycaemia - inhibition of insulin and stimulation of glucagon

Question 8

What is the effect of glucocorticoids on lipid metabolism?

Answer 8

redistribution of body fat

= increased lipolysis by adipocytes

Question 9

What is the effect of glucocorticoids on the cardiovascular system?

Answer 9

hypertension

Question 10

What is the effect of glucocorticoids on the immune system?

Answer 10

immunosuppression:

• redistribution of leukocytes
• maintenance of lymphoid tissue

Question 11

What is the effect of glucocorticoids on the skeletal system?

Answer 11

maintenance of muscular tone

Question 12

What is the effect of glucocorticoids on CNS?

Answer 12

regulation of neuronal excitability

Question 13

Where are glucocorticoids receptors found? What forms do these receptors come in?

Answer 13

found in the cytoplasm and nucleus of most cells
2 main forms:
1. alpha: bind steroids (777aa)
2. beta: does not bind steroids, binds DNA (742aa)
–> predominant form

*steroids bind to the C terminal of GRs

Question 14

What are the genomic activities of glucocorticoid receptors?

Answer 14

• transactivation of gene transcription by direct interaction with DNA
• transrepression by interaction with other proteins in cytoplasm or nucleus
• -> corticosteroids can switch off the ability of TNF alpha to bind to promoter sequences that stimulate pro-inflammatory signals by bind to them and changing their affinity to these promotor regions

Question 15

What are the non-genomic activities of glucocorticoid receptors?

Answer 15

1. interaction of GC with plasma membrane GR –> signal to cytoplasmic GRs
2. interaction of GC with cytoplasmic GR –> activated in the cytoplasm –> stimulates the SRC –> upregulation of transcription factors
3. interaction of GC with membrane –> intercalate with membrane –> stop receptors moving together –> downregulates the cell’s function

Question 16

How are glucocorticoids associated with Addisonian crises?

Answer 16

Group of symptoms that indicate severe adrenal insufficiency caused by insufficient cortisol levels
–> can be the result of suddenly stopping glucocorticoids (adrenal cortex regresses, shrivels up and stops producing cortisol)

Question 17

What are the symptoms of an Addisonian crisis?

Answer 17

• Sudden penetrating pain in the legs, lower back, or abdomen
• Severe vomiting and diarrhea, resulting in dehydration
• Low blood pressure
• Syncope (loss of consciousness and ability to stand)
• Hypoglycemia (reduced level of blood glucose)
• Confusion, psychosis, slurred speech
• Severe lethargy
• Hyponatremia (low sodium level in the blood)
• Hyperkalemia (elevated potassium level in the blood)
• Hypercalcemia (elevated calcium level in the blood)
• Convulsions
• Fever