Steroids of the adrenal cortex

Question 1

What are the steroids of the adrenal cortex?

Answer 1

Glucocorticoids: principally cortisol in mammals
Mineralocorticoids: aldosterone
Androgens (sex hormones precursors)

Question 2

What is cortisol?

Answer 2

Stress hormone but essential to life

Metabolic, cardiovascular and immune functions

Question 3

What is aldosterone?

Answer 3

Maintains blood volume by regulating the amount of body sodium

Question 4

How does blood flow in the adrenal gland?

Answer 4

From the outer cortex to the inner medulla

Question 5

What are the different zones in the cortex, top to bottom?

Answer 5

Zona glomerulosa
Zona fasciculata
Zona reticularis

Question 6

What do the three zones secrete?

Answer 6

Zona glomerulosa - Mineralocorticoids (aldosterone)
Zona fasciculata - Glucocorticoids (cortisol)
Zona reticularis - Adrenal androgens

Question 7

What molecule does steroid hormone synthesis always start off as?

Answer 7

Cholesterol

Question 8

What are layer-specific enzymes?

Answer 8

They are different enzymes in different layers that determine the metabolic pathway of cholesterol about which steroid hormone it makes, depending on where the cholesterol ends up in the adrenal cortex

Question 9

What are the functions of mineralocorticoid?

Answer 9

Sodium retention (whole body sodium)
Active reabsorption of sodium (with associated passive reabsorption of water)
Active secretion of potassium 
Volume regulation (part of RAAS)

Note: increased MC activity increases the amount of sodium retained in the body, not the concentration. This is because an osmotically-equivalent amount of water is retained with the sodium, so the concentration doesn’t change

Question 10

How does the control of aldosterone secretion work?

Answer 10

If a drop in perfusion pressure is detected, due to lower blood volume or sodium, will be detected in the kidney itself. Specialised epithelial cells will trigger a sequence of events which will lead to the release of aldosterone.

Question 11

As cortisol and aldosterone have similar affinity for the aldosterone receptor, why doesn’t circulating concentrations of cortisol, which is much higher than aldosterone, stimulate salt and water retention?

Answer 11

Cortisol is rapidly metabolized to inactive cortisone in the kidney

Requires enzyme, 11beta-hydroxysteroid dehydrogenase type 2

Question 12

Describe the glucocorticoid receptor

Answer 12

Member of the nuclear receptor superfamily

Characteristic 3-domain structure
-Ligand-binding
-DNA-binding (binds to HRE on genomic DNA)
-N-terminal transcription cofactor-binding
Receptors dimerize on ligand binding and translocate to the nucleus

Question 13

What are the metabolic functions of glucocorticoids?

Answer 13

Decreased glucose utilization (glucose sparing)

• Proteolysis
• Gluconeogenesis (mainly from amino acids)
• Lipolysis

Overall: maintenance of blood glucose – essential for survival during fasting

Question 14

What are the cardiovascular functions of glucocorticoids?

Answer 14

Required for vascular integrity and maintenance of blood pressure

hypocortisolism: inappropriate vasodilation, hypotension
hypercortisolism: hypertension

Question 15

What are the immune functions of glucocorticoids?

Answer 15

Anti-inflammatory and immunosuppressive

Question 16

What kind of receptor is an ACTH receptor?

Answer 16

G-protein coupled, via cAMP stimulates cholesterol uptake and steroid synthesis

Question 17

What are the causes of adrenal insufficiency?

Answer 17

Addison’s disease: primary adrenal insufficiency
Secondary (hypopituitarism; secondary to failure in RAAS)
Enzyme defect in steroid synthesis pathways

Question 18

What are the clinical features of Addison’s disease?

Answer 18

Primary adrenal insufficiency
-Low circulating adrenal steroids, e,g. cortisol, androgens and aldosterone
-High ACTH
-Plasma [Na+]: normal to low
-Plasma [K+]: normal to high
-Elevated plasma renin
May be unmasked by significant stress or illness – shock, hypotension, volume depletion (adrenal crisis)

Question 19

What forms of hypercortisolism can you get?

Answer 19

Cushing’s syndrome: excess glucocorticoid

ACTH-dependent

• Cushing’s disease: due to increased ACTH secretion (typically due to pituitary adenoma: secondary)
• Ectopic ACTH-secreting tumour

ACTH-independent

• Adrenal adenoma or carcinoma (primary)
• Iatrogenic; effect of GC therapy

Question 20

What are the clinical features of hypercortisolism?

Answer 20

Hypertension 
Hyperglycaemia 
Truncal obesity
Fatigue, muscle weakness
Virilization (hirsutism in females)
Depression, mood or psychiatric disturbances