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PT4023 CA1 > L3 Glucocorticoids > Flashcards

L3 Glucocorticoids Flashcards

1
Q

How are adrenocorticoids regulated?

A

by adrenocorticotropic hormone (ACTH)

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2
Q

What are adrenocorticoids synthesised from?

A

a cholesterol backbone

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3
Q

Two subcategories of adrenocorticoids:

A

Mineralocorticoids and glucocorticoids

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4
Q

Steroid hormones produced by adrenal cortex

A
  1. Mineralocorticoids (aldosterone)
  2. Glucocorticoids (cortisol)
  3. Adrenal androgens (testosterone)
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5
Q

Adrenal medulla produces __.

A

catecholamines e.g. adrenaline and noradrenaline

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6
Q

Which zone of the adrenal cortex secretes mineralocorticoids?

A

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

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7
Q

What does the inner zone of adrenal cortex secrete?

A

glucocorticoids (zona fasciculata) and androgens (zona reticularis)

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8
Q

What does the inner zone of the adrenal cortex express?

A

17α-hydroxylase and 11β-hydroxylase

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9
Q

ACTH is synthesised from __.

A

pro-opiomelanocortin (POMC)

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10
Q

What is the 2nd messenger for most steroidogenesis?

A

cyclic AMP

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11
Q

3 levels of regulation of ACTH secretion

A
  • diurnal rhythm in basal steroidogenesis
  • negative feedback regulation
  • marked increases in steroidogenesis in response to stress
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12
Q

90% of glucocorticoids are bound to?

A

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

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13
Q

CBG elevated in?

A

pregnancy, hyperthyroidism, oestrogen admin

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14
Q

CBG diminished in?

A

hypothyroidism, protein deficiency, genetic defects

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15
Q

Examples of adrenal androgens that have androgenic-oestrogenic activity

A

Dehydroepiandrosterone (DHEA) and androstenedione

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16
Q

Indications of DHEA and androstenedione

A
  • SLE
  • women with adrenal insufficiency
17
Q

Glucocorticoids MOA

A
  • bind to cytosol receptors (steroid-receptor complex)
  • alters gene expression by binding to glucocorticoid-response element (GRE)
  • initiate an anti-inflammatory response
18
Q

Physiological effect of aldosterone

A

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

19
Q

Which immune cells do glucocorticoids act on?

A

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

20
Q

Short-intermediate acting glucocorticoids

A

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

21
Q

Intermediate-acting glucocorticoids

A
  • Triamcinolone
  • Paramethasone
  • Fluprednisolone
22
Q

Long-acting glucocorticoids

A
  • Betamethasone
  • Dexamethasone
23
Q

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

A

medulla is highly vascular

24
Q

Synthesis pathway of mineralocorticoids

A

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

25
Q

Synthesis pathway of glucocorticoids

A

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

26
Q

Synthesis pathway of sex steroids

A

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)

27
Q

What enzyme converts testosterone to estradiol?

A

CYP19A1 (aromatase, oestrogen synthase)

28
Q

What part of the day are cortisol levels very high?

A

When you wake up in the morning

29
Q

Where is cortisol metabolised and what is it converted to?

A

cortisol is metabolised in the liver to glucuronic acid or sulphates

30
Q

Cortisol half-life

A

60-90 mins (very short)

31
Q

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

A

10-20mg/day
dependent on circadian rhythm

32
Q

What are glucocorticoids the first port of call for?

A

a significant immune response

33
Q

Physiological effects of glucocorticoids

A
  • 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
34
Q

Indications of long-acting glucocorticoids

A

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

PT4023 CA1 (8 decks)

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