Endo: Adrenal Cortex

Question 1

What four enzymes are required for cortisol synthesis?

Answer 1

• 20-22 desmolase
• 17alpha hydroxylase
• 21 hydroxylase
• 11beta hydroxylase

Question 2

What step in cortisol synthesis is rate limiting?

Answer 2

Conversion of cholesterol to pregnenalone by 20-22 desmolase

Question 3

What enzymes are required for aldosterone synthesis? (3)

Answer 3

• 20-22 desmolase
• 21 hydroxylase
• 11beta hydroxylase

Question 4

What enzymes are required for androgen synthesis? (2)

Answer 4

20-22 desmolase

17alpha hydroxylase

Question 5

Adrenal cortex is derived from ________

Adrenal medulla is derived from _______

Answer 5

Adrenal cortex is derived from mesoderm

Adrenal medulla is derived from neural crest (ectoderm)

Question 6

What is made in each layer of the adrenal gland?

Answer 6

• Cortex
  
  • Glomerulosa: aldosterone
  • Fasiculata: cortisol
  • Reticulata: androgen
• Medulla: epi, norepi

Question 7

How is cortisol transported in the blood?

Answer 7

Cortisol is bound to cortisol-binding-protein when in the blood

*b/c it’s lipophilic!

Question 8

Compare the timeline for cortisol and epi

Answer 8

Cortisol is a long-acting stress hormone

Epi is a short-acting stress hormone

Question 9

A patient’s total cortisol is elevated. Is this problematic?

Answer 9

NO. Total cortisol doesn’t matter

Only free cortisol exerts an effect

Question 10

Describe what happens when cortisol reaches its target cell (signaling pathway)

Answer 10

1. Cortisol receptor exists in the cytoplasm bound to HSP-90
2. Cortisol diffuses across cell membrane and binds to its receptor
3. The receptor releases HSP-90 and dimerizes
4. Receptor-cortisol complex then translocates to nucleus
5. Changes gene expression

Question 11

How does cortisol exert its anti-inflammatory action?

Answer 11

Cortisol inhibits Phospholipase A2

Without PLA2, no arachidonic acid is produced and neither leukotrienes nor prostaglandins can be made

Question 12

Describe the effects of cortisol

Answer 12

• Appetite increases
• Blood pressure and heart rate increases
• Insulin resistence
• Gluconeogenesis, proteolysis, fat lipolysis
• Fibroblast suppression
• Inflammation and immune suppression
• Bone formation decreases

Question 13

How does cortisol cause an increase in heart rate and blood pressure?

Answer 13

Cortisol has a permissive effect on epi

Question 14

Why do patients with excess cortisol have thin skin?

Answer 14

Fibroblasts are suppressed, so can’t produce collagen

Question 15

Describe the fat changes that occur with excess cortisol

Answer 15

Cortisol causes a redistribution of fat from periphery to central

This creates buffalo hump and moon facies

Question 16

Describe the serum cell counts seen in cortisol excess (3)

Answer 16

• Increased neutrophils (b/c neutrophils can’t get out of vessels)
• Decreased B/T cells
• Decreased eosinophils

Question 17

Describe the HPA axis for cortisol, including feedback

Answer 17

1. Hypothalamus makes CRH
2. CRH stimulates anterior pituitary to make ACTH
3. ACTH stimulates adrenal to make cortisol
4. Cortisol feeds back and inhibits hypothalamus

Question 18

How does CRH exert its effects?

Answer 18

CRH (released by hypothalamus) cleaves POMC in the anterior pituitary. This cleavage releases ACTH

Question 19

What is Addison’s disease?

What levels of ACTH, cortisol, and aldosterone are seen?

Answer 19

• Addison’s = autoimmune destruction of adrenal gland
• Elevated ACTH
• Low cortisol and aldosterone

Question 20

What levels of ACTH, cortisol, and aldosterone are seen in hypopituitarism?

Answer 20

• Low ACTH
• Low cortisol
• Normal aldosterone (b/c it can be regulated by renin-angiotensin system)

Question 21

What is Cushing’s disease?

What levels of ACTH, cortisol, and aldosterone are seen?

Answer 21

• Cushing’s disease is an ACTH-secreting pituitary adenoma
• ACTH is elevated
• Cortisol is elevated
• Aldosterone is normal (b/c it’s regulated by renin-angiotensin)