Adrenocorticosteroids

Question 1

Adrenal Gland (made up of? and which hormones?)

Answer 1

1. medulla - adrenaline, catecholamine/amino acid hormone
2. cortex - zona glomerulosa, zona fasciculata, zona reticularis, steroid hormones

Question 2

mineral corticoids functions

Answer 2

salt balance, aldosterone, zone glomeculosa

Question 3

glucocorticoids functions

Answer 3

metabolic and immune effects, cortisol, zona fasciculata

Question 4

androgens functions

Answer 4

DHEA, precursors for strong androgens (testosterone) and estrogens, zona reticularis

Question 5

‘HPA’ Axis

Answer 5

controls cortisol release from the zona fasciculata

Question 6

Steroidgenesis

Answer 6

ACTH (pituitary) stimulates steroid production
- after meals
-circadian rhythm
ACTH is controlled by CRH from the hypothalamus

Question 7

T/F - steroid hormones can be stored like peptides

Answer 7

false, ACTH stimulates cortisol synthesis

Question 8

Where does Cortisol exert negative feedback on?

Answer 8

CRH (hypothalamus)
ACTH ( ant. pituitary)

Question 9

Negative Feedback in the HPA axis

Answer 9

• cortisol suppresses stress signals like cytokines involved in the stress response
• cortisol acts on glucocorticoid target tissues - stress response, catabolism and immunosuppression

Question 10

What does RAAS stand for?

Answer 10

renin-angiotensin- aldosterone- system

Question 11

Explain RAAS

Answer 11

• renin: released by the juxtaglomerular apparatus (kidney) generates AT1 from angiotensin
• ACE (angiotensin converting enzyme) converts AT1 to AT2
• AT2 triggers aldosterone release

Question 12

Function of Aldosterone

Answer 12

primary target is the kidneys, promotes Na+/water reabsorption, K+ excretion, ‘mineralcorticoid response’

Question 13

Primary Role of RAAS

Answer 13

control blood pressure/volume

Question 14

Generalized Mechanism of Steroid Hormone Action

Answer 14

• cytoplasmic unliganded receptor in complex Hsp90
• binding of hormone causes dissociation from Hsp, transport into nucleus
• dimerized receptors, interact with DNA and influence transcription of target genes

Question 15

GRE

Answer 15

glucocorticoid response element

Question 16

Receptors for Corticosteroids

Answer 16

1. glucocorticoid receptor (stimulates GC response)
2. mineral corticoid receptor (stimulates MC response)

Question 17

‘Spectrum’

Answer 17

steroids have different affinities for either receptor
- each receptor activates/represses transcription of different sets of genes (and unique target tissues)

Question 18

Pseudohyperaldosteronism (licorice)

Answer 18

licorice contains an inhibitor of 11(beta)-hydroxysteroid dehydrogenase, type 2
- this allows glucocorticoids to have an inappropriate effect in aldosterone target tissues like the kidney
- a licorice overdose can cause high blood pressure

Question 19

Apparent Mineralcorticoid Excess (what is it?)

Answer 19

genetic disease arising from mutations in the 11(beta)-hydroxysteroid dehydrogenase, type 2 gene

Question 20

Metabolic Effects of GLUCOcorticoids

Answer 20

carbohydrate metabolism - increases circulating glucose
fat/lipid balance - promotes fat deposition in the trunk but fat breakdown in the limbs
- overall catabolic effects, loss of muscle and bone in the limbs

Question 21

Anti-Inflammatory Effects of GLUCOcorticoids

Answer 21

key glucocorticoid-mediated mechanisms in inflammation:
- inhibit AA generation
- inhibit prostanoid synthesis
these two effects have widespread downstream effects on inflammatory systems

Question 22

COX-2 Suppression

Answer 22

-COX-2 is an important inflammatory mediatory, early in the process of inflammation
- COX-2 plays an early step in metabolism of Arachadonic Acid to various prostanoids
-glucocorticoid regulation of COX-2 does not involve direct receptor antagonism
glucocorticoids influence (suppress) transcription of the COX-2 gene, leading to a longterm suppression of COX-2 expression (protein levels)

Question 23

Annexin A-1 (role in anti-inflammatory)

Answer 23

1. direct effects of Leukocytes inhibits their tissue inflammation
2. suppression on phospholipase A2 activity- this prevents aa generation and thereby suppresses downstream generation of prostanoids

Question 24

In a patient undergoing treatment with a therapeutic dose of a glucocorticoid
like dexamethasone, which of the following would be expected?
A. Elevated circulating levels of ACTH/corticotropin
B. Hypoglycemia
C. Hyperplasia (increased size) of the adrenal gland
D. Reduced circulating levels of corticotropin-releasing factor (i.e. CRF or CRH)
E. Enhanced production of endogenous cortisol

Answer 24

D

Question 25

Lipocortin Induction

Answer 25

effects of annexin A-1 are very early in the inflammatory response
- lipocortin is a protein - expression is induced by GC receptor activation

Question 26

Addison’s Disease

Answer 26

• chronic adrenocortical insufficiency (fatigue, salt balance, sugar balance problems, skin discoloration)
• low production of glucocorticoids and often mineralcorticoids
• typically treated with GC/MC supplementation (hydrocortisone/cortisol)

Question 27

Cunning’s Syndrome

Answer 27

• adrenal overactivity leading to excessive cortisol
• round face, fat deposition in the trunk
• muscle loss, osteoporosis
• resection of adrenals of pituitary tumor, followed by gradual adjustment towards a maintenenace dose of cotisol
  symptoms resemble side effects of therapeutic doses of GC’s

Question 28

Glucocorticoids as Therapeutics

Answer 28

powerful anti-inflammatory, immunosuppressive actions of cortisol and analogs
(addison-like symptoms if stopped abruptly)

Question 29

Side effects of Glucocorticoid Treatment

Answer 29

metabolic
- hyperglycemia
- care must be taken with diabetic patients

immunosuppressive
- caution with patients carrying infections
- latent infections can emerge (TB)

catabolic
- osteoporosis, muscle wasting

anti-inflammatory
- slow wound nesting, ulcerations
- cushingoid, tapering

other