L3 Glucocorticoids

Question 1

How are adrenocorticoids regulated?

Answer 1

by adrenocorticotropic hormone (ACTH)

Question 2

What are adrenocorticoids synthesised from?

Answer 2

a cholesterol backbone

Question 3

Two subcategories of adrenocorticoids:

Answer 3

Mineralocorticoids and glucocorticoids

Question 4

Steroid hormones produced by adrenal cortex

Answer 4

1. Mineralocorticoids (aldosterone)
2. Glucocorticoids (cortisol)
3. Adrenal androgens (testosterone)

Question 5

Adrenal medulla produces __.

Answer 5

catecholamines e.g. adrenaline and noradrenaline

Question 6

Which zone of the adrenal cortex secretes mineralocorticoids?

Answer 6

outer zone (zona glomerulosa), receptors for angiotensin II and express aldosterone synthase

Question 7

What does the inner zone of adrenal cortex secrete?

Answer 7

glucocorticoids (zona fasciculata) and androgens (zona reticularis)

Question 8

What does the inner zone of the adrenal cortex express?

Answer 8

17α-hydroxylase and 11β-hydroxylase

Question 9

ACTH is synthesised from __.

Answer 9

pro-opiomelanocortin (POMC)

Question 10

What is the 2nd messenger for most steroidogenesis?

Answer 10

cyclic AMP

Question 11

3 levels of regulation of ACTH secretion

Answer 11

• diurnal rhythm in basal steroidogenesis
• negative feedback regulation
• marked increases in steroidogenesis in response to stress

Question 12

90% of glucocorticoids are bound to?

Answer 12

corticosteroid-binding globulin (CBG)
(5% bound to albumin, remainder is free)

Question 13

CBG elevated in?

Answer 13

pregnancy, hyperthyroidism, oestrogen admin

Question 14

CBG diminished in?

Answer 14

hypothyroidism, protein deficiency, genetic defects

Question 15

Examples of adrenal androgens that have androgenic-oestrogenic activity

Answer 15

Dehydroepiandrosterone (DHEA) and androstenedione

Question 16

Indications of DHEA and androstenedione

Answer 16

• SLE
• women with adrenal insufficiency

Question 17

Glucocorticoids MOA

Answer 17

• bind to cytosol receptors (steroid-receptor complex)
• alters gene expression by binding to glucocorticoid-response element (GRE)
• initiate an anti-inflammatory response

Question 18

Physiological effect of aldosterone

Answer 18

enhanced reabsorption of sodium, leading to water retention and increased blood volume

Question 19

Which immune cells do glucocorticoids act on?

Answer 19

neutrophils (stabilise lysosomal membranes), mast cells (inhibit histamine, PG & leukotriene release), T lymphocytes (suppress activation), macrophages (decrease activation), eosinophils (increase transcription of annexin-1)

Question 20

Short-intermediate acting glucocorticoids

Answer 20

hydrocortisone (cortisol), cortisone, prednisone, prednisolone, methylprednisolone, meprednisone

Question 21

Intermediate-acting glucocorticoids

Answer 21

• Triamcinolone
• Paramethasone
• Fluprednisolone

Question 22

Long-acting glucocorticoids

Answer 22

• Betamethasone
• Dexamethasone

Question 23

What characteristic of the adrenal medulla facilitates rapid production of adrenaline in response to stress (HPA axis)?

Answer 23

medulla is highly vascular

Question 24

Synthesis pathway of mineralocorticoids

Answer 24

Cholesterol –> pregnenolone (via CYP11A1) –> progesterone (via 3βHSD) –> deoxycorticosterone (via CYP21) –> corticosterone (via CYP11B1) –> aldosterone (CYP11B2)

Question 25

Synthesis pathway of glucocorticoids

Answer 25

Cholesterol --> pregnenolone (via CYP11A1) --> 17α-hydroxypregnenolone (via CYP17A1 and 17α-hydroxylase) --> 17α-hydroxyprogesterone (via 3βHSD) --> deoxycortisol (via CYP21) --> cortisol (via CYP11B1)

Question 26

Synthesis pathway of sex steroids

Answer 26

Cholesterol --> pregnenolone (via CYP11A1) --> 17α-hydroxypregnenolone (via CYP17A1 and 17α-hydroxylase) --> DHEA (via CYP17A1 and 17,20 lyase) --> androstenedione (via 3βHSD) --> (i) estrone (via CYP19A1) --> estradiol (via 17βHSD1), or (ii) testosterone (via 17βHSD3)

Question 27

What enzyme converts testosterone to estradiol?

Answer 27

CYP19A1 (aromatase, oestrogen synthase)

Question 28

What part of the day are cortisol levels very high?

Answer 28

When you wake up in the morning

Question 29

Where is cortisol metabolised and what is it converted to?

Answer 29

cortisol is metabolised in the liver to glucuronic acid or sulphates

Question 30

Cortisol half-life

Answer 30

60-90 mins (very short)

Question 31

How much cortisol is produced daily, and what is production dependent on?

Answer 31

10-20mg/day dependent on circadian rhythm

Question 32

What are glucocorticoids the first port of call for?

Answer 32

a significant immune response

Question 33

Physiological effects of glucocorticoids

Answer 33

- stimulate gluconeogenesis - ↑Na+ reabsorption, H2O excretion, ↓Ca2+ uptake, ↑Ca+ excretion - increased protein breakdown - redistribution of body fat, lipogenesis - steroid myopathy is a potential adverse effect

Question 34

Indications of long-acting glucocorticoids

Answer 34

Tend to be given to patients with very significant inflammatory responses e.g. rheumatoid arthritis and Crohn's disease (relapses)