Adrenocorticosteroids Flashcards
what hormone does the adrenal medulla produce?
adrenaline (catecholamine/aa hormone)
what type of hormones does the adrenal cortex produce?
steroid hormones (cholesterol-derived, lipid-soluble)
what are the 3 zones of the adrenal cortex? (out to in)
zona glomerulosa, zona fasciculata, zona reticularis
what zona secretes mineralocorticoids (aldosterone)?
zona glomerulosa (outer layer)
what zona secretes glucocorticoids (cortisol)?
zona fasciculata (middle)
what zona secretes androgens (DHEA)?
zona reticularis
what is the purpose of hormones secreted from the zona glomerulosa, fasciculata, and reticularis resp.?
glom: salt balance (salt)
fasc: metabolism and immunity (sugar)
ret: androgen/estrogen precursors (sex)
what does the HPA (hypothal-ant pit axis) stimulate for cortisol release?
zona fasciculata
what hormone stimulates steroid production/cortisol release from adrenal cortex?
adrenocorticotropic releasing hormone (ACTH)
where is ACTH released from?
anterior pituitary
when is ACTH released from the ant pit?
after meals, before waking (has circadian rhythm)
what hormone controls ACTH?
corticotropin-release hormone/factor (CRH/CRF)
where is CRH/CRF released from?
hypothalamus
how are steroid hormones stored?
are not stored, but synthesized and released when needed (ACTH triggers cortisol synthesis)
what does cortisol exert neg feedback on? (2)
CRH (hypo) and ACTH (ant pit)
t/f: cortisol cannot suppress synthesis of other stress signals (cytokines) that can stimulate cortisol HPA?
false, cortisol can suppress stress signals such as cytokines
what is the glucocorticoid response?
changes in stress response, catabolism, and immunosuppression in glucocorticoid target tissues from cortisol
where is renin secreted from?
juxtaglomerular apparatus (in kidney)
what does AT2 act on?
AT2 receptors in adrenal cortex to trigger aldosterone release
what is the mineralocorticoid response?
Na/H2O reabsorption and K excretion in kidney from aldosterone
what is the primary role of the RAAS system?
control of blood pressure and volume
what is the chaperone for the generalized cytoplasmic steroid hormone receptor?
Hsp90 (heat shock protein)
what is the effect of ligand binding to cytoplasmic receptors? (2)
Hsp dissociation, dimerization of steroid-receptor complex, transport into nucleus, influence of transcription in target genes
what is the glucocorticoid response element (GRE)?
genes targeted by glucocorticoids (in complex w receptor and dimerized)
what are 2 key gene products of GR binding?
lipocortin and COX-2
what allows diff physl responses to glucocorticoids (GC response) and mineralocorticoids (MC response)?
diff receptors which target diff response elements
what ratio does cortisol bind to glucocorticoid vs mineralocorticoid receptors?
1:1
how do corticosteroids exhibit a spectrum of effects?
have diff affinities for either GC or MC receptor
t/f: GC and MC receptors activate/repress transcription of diff genes
true
what enzyme do glucocorticoid target tissues (adipose, muscle, liver) express? function?
11B-hydroxysteroid dehydrogenase, TYPE 1 (HSD1); converts cortisone (inactive) to cortisol (active)
what does glucocorticoid target tissues having HSD1 suggest about cortisol specificity?
can be regulated by metabolism in target tissues (as well as affinity to receptor)
what is the diff btwn prednisone vs prednisolone?
prednisone: not effective topically/inactive glucocorticoid
prednisolone: effective topically/active form of prednisone
what is the best way to administer prednisone? why?
orally (vs topically); first metabolism/tissue enzymes activate it to prednisolone
why does cortisol have weak mineralocorticoid effects in vivo if it activates GR and MR?
mineralocorticoid target tissues (kidney cells) express 11B-hydroxysteroid dehydrogenase, TYPE 2 (HSB2) that converts cortisol to cortisone (inactivates it)
what does licorice contain? effect?
inhibitor to HSB2 which allows cortisol (glucocorticoid) to affect aldosterone (mineralocorticoid) target tissues (kidneys) and cause high BP (Na/H2O retention)
what is apparent mineralocorticoid excess disease? effect?
mutations in HSB2 gene which decr its activity and incr activation of MR in kidneys by cortisol (GC), incr BP
how do glucocorticoids (cortisol) incr circulating glucose levels? (2)
incr gluconeogenesis and release from liver, inhibits insulin in muscle and adipose (prevents glucose uptake
how do glucocorticoids (cortisol) affect fat/lipid balance?
incr lipolysis in limbs but fat deposition in viscera/trunk area (“skinny fat”)
what is the overall catabolic effect of cortisol?
loss of muscle and bone mass in limbs
what are the 2 inflammatory mechanisms affected by glucocorticoids (cortisol)?
inhibits phospholipase A2/arachidonic acid synthesis and inhibits cyclo-oxygenase 2 (COX-2)/prostanoid synthesis
what are 2 actions of COX-2?
inflammatory mediator that plays an early step in metabolism of arachidonic acid into prostanoids
how do glucocorticoids inhibit COX-2?
suppress COX-2 gene transcription (long-term) - don’t directly inhibit COX-2/receptor
what are lipocortins/annexins?
family of proteins that have “annexin repeats”
how does annexin A-1 (gene) exhibit anti-inflammatory effects? (2)
prevents WBC infiltration into tissues and suppresses phospholipase A2 activity (prevents arachidonic acid/prostanoid synth)
what induces expression of lipocortin/annexin A-1?
glucocorticoid receptor activation
what is Addison’s disease?
chronic adrenocortical insufficiency, decr glucocorticoid (cortisol) and mineralocorticoid (aldosterone) synthesis
what are 4 symptoms of Addison’s disease?
fatigue, salt and sugar imbalances, skin discolouration
how is Addison’s disease treated?
GC/MC supplements (hydrocortisone)
what is Cushing’s syndrome?
adrenal overactivity leading to excessive cortisol
what are 4 potential causes of Cushing’s syndrome?
adrenal tumour (cortisol producing), pituitary tumour (ACTH producing), drug-induced (chronic GC treatment), ectopic tumour (ACTH producing)
what are 3 symptoms of Cushing’s syndrome?
round face/fatty trunk, muscle loss, osteoporosis (protein and bone catabolism)
what is a potential treatment for Cushing’s syndrome?
resection of adrenal/pituitary tumour and adjustment of cortisol levels
what are 8 possible therapeutic purposes for glucocorticoids?
anti-inflammatory/immunosuppressant, allergic rxns, eye inflammation, pain/scarring reduction, GI disease (IBS), hematological disorders (leukemia, myeloma), asthma, organ transplant (avoid rejection)
what symptoms may occur if GC supplements are stopped abruptly?
Addison-like symptoms/’Addisonian’ crisis: hypoglycemia, hyperkalemia, hyponatremia (low Na), low BP
what causes Addison-like symptoms/’Addisonian’ crisis when GC supplements are stopped abruptly?
negative feedback from GC supplememnts suprresses CRH and ACTH, therefore decr levels wo/ GC causes decr cortisol levels and side effects
what is a way to prevent side effects when stopping long-term GC use?
tapering (dont stop abruptly)
what 9 side effects of GC treatment?
hyperglycemia, opportunistic/latent infections, osteoporosis, muscle wasting, slow wound healing, ulcerations, hypertension, psychosis, ‘Cushingoid’ (fat redistribution)
