Adrenocorticosteroids Flashcards
(29 cards)
Adrenal Gland (made up of? and which hormones?)
- medulla - adrenaline, catecholamine/amino acid hormone
- cortex - zona glomerulosa, zona fasciculata, zona reticularis, steroid hormones
mineral corticoids functions
salt balance, aldosterone, zone glomeculosa
glucocorticoids functions
metabolic and immune effects, cortisol, zona fasciculata
androgens functions
DHEA, precursors for strong androgens (testosterone) and estrogens, zona reticularis
‘HPA’ Axis
controls cortisol release from the zona fasciculata
Steroidgenesis
ACTH (pituitary) stimulates steroid production
- after meals
-circadian rhythm
ACTH is controlled by CRH from the hypothalamus
T/F - steroid hormones can be stored like peptides
false, ACTH stimulates cortisol synthesis
Where does Cortisol exert negative feedback on?
CRH (hypothalamus)
ACTH ( ant. pituitary)
Negative Feedback in the HPA axis
- cortisol suppresses stress signals like cytokines involved in the stress response
- cortisol acts on glucocorticoid target tissues - stress response, catabolism and immunosuppression
What does RAAS stand for?
renin-angiotensin- aldosterone- system
Explain RAAS
- renin: released by the juxtaglomerular apparatus (kidney) generates AT1 from angiotensin
- ACE (angiotensin converting enzyme) converts AT1 to AT2
- AT2 triggers aldosterone release
Function of Aldosterone
primary target is the kidneys, promotes Na+/water reabsorption, K+ excretion, ‘mineralcorticoid response’
Primary Role of RAAS
control blood pressure/volume
Generalized Mechanism of Steroid Hormone Action
- 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
GRE
glucocorticoid response element
Receptors for Corticosteroids
- glucocorticoid receptor (stimulates GC response)
- mineral corticoid receptor (stimulates MC response)
‘Spectrum’
steroids have different affinities for either receptor
- each receptor activates/represses transcription of different sets of genes (and unique target tissues)
Pseudohyperaldosteronism (licorice)
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
Apparent Mineralcorticoid Excess (what is it?)
genetic disease arising from mutations in the 11(beta)-hydroxysteroid dehydrogenase, type 2 gene
Metabolic Effects of GLUCOcorticoids
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
Anti-Inflammatory Effects of GLUCOcorticoids
key glucocorticoid-mediated mechanisms in inflammation:
- inhibit AA generation
- inhibit prostanoid synthesis
these two effects have widespread downstream effects on inflammatory systems
COX-2 Suppression
-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)
Annexin A-1 (role in anti-inflammatory)
- direct effects of Leukocytes inhibits their tissue inflammation
- suppression on phospholipase A2 activity- this prevents aa generation and thereby suppresses downstream generation of prostanoids
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
D
