3 - adrenocorticosteroids Flashcards
where is adrenaline released? (cortex or medulla)
medulla
where are steroid hormones released? (cortex or medulla)
cortex
what are the three layers for the adrenal cortex
zone glomerulosa, fasciculata, reticularis
where is catecholamine/aa hormone released? (cortex or medulla)
medulla
where are mineralocorticoids released
zone glomerulosa
where are glucocorticoids released
zone fasciculata
where are andogens released
zone reticularis
name an example of a mineralocorticoid
aldosterone
name an example of a glucocorticoid
cortisol
name an example of an androgen
DHEA
what is DHEA
precursor for strong androgens (testosterone) and estrogens
what is the order going inwards of the 4 layers of the adrenal gland
zone glomerulosa, fasciculata, reticularis, adrenal medulla
what is the role of mineralocorticoids
salt balance
what is the role of glucocorticoids
metabolic and immune effects
what is the common precursor for all adrenal steroids
cholesterol
what is the HPA axis
hypothalamus, anterior pituitary, adrenal cortex
what does the HPA axis control
cortisol release from the zona fasciculata
where is ACTH released from
the anterior pituitary
what does ACTH stimulate
steroid production
when is ACTH stimulated
after meals, just before waking (circadian rhythm)
where is CRH released from
hypothalamus
what is ACTH released controlled by
CRH from the hypothalamus
what kind of hormone is cortisol
steroid
how are steroid hormones stores
cant be stored in vesicles, regulated at point of synthesis
lipophilic
what stimulates cortisol synthesis
ACTH
where does cortisol give negative feedback to and what does it cause
(where and what is less released)
onto the hypothalamus and anterior pituitary to reduce the release of CRH and ACTH
what does ACE do
converts AT1 to AT2
what does AT2 trigger
aldosterone release
what is the role of aldosteron
promotes sodium and water reabsorption in the kidneys
what is the mineralocorticoid response
water and sodium reabsorption
what is the primary role of the RAAS
control of blood pressure and volume
what is GRE and what does it do
glucocorticoid receptor/response element
what happens once a steroid hormone binds to its receptor
the receptor dissociates from Hsp90 complex, transport to nucleus, change gene transcription
what is the spectrum of receptors for corticosteroids
some have more affinities for glucocorticoids while others have affinities for mineralocorticoids
what does 11beta-hydroxysteroid dehydrogenase type 1 do?
it activates cortisol
turns it from a ketone to an alcohol
what does corticosteroid specificity arise from? (2 things)
affinity to receptor and metabolism in target tissues (11beta-hydroxysteroid dehydrogenase)
where is there a lot of 11beta-hydroxysteroid dehydrogenase type 1
in glucocorticoid target tissues (adipose, muscle, liver)
is prednisone or prednisolone better to take topically and why
prednisolone because it is the active form (has an OH group)
can prednisone work orally
yes, it is metabolized to prednisolone in the liver and in glucocorticoid receptor tissues
which receptors does cortisol have affinity for
same affinity for glucocorticoid and mineralocorticoid receptors
why does cortisol have weak mineralocorticoid effects
kidney cells (mineral.. targets) have [11beta-hydroxysteroid dehydrogenase type 2] which inactivates cortisol
where is there 11beta-hydroxysteroid dehydrogenase type 2
in cells that dont want cortisol to work
what is pseudohypoeraldosteronism
when cortisol affects the aldosterone target tissues (mineralocorticoid)
how does pseudohypoeraldosteronism happen
11beta-hydroxysteroid dehydrogenase type 2 is inhibited by something like licorice
what is apparent mineralocorticoid excess
mutations in 11beta-hydroxysteroid dehydrogenase type 2
what does glucocorticoids do to carbohydrate metabolism and glucose
increases circulating glucose
do glucocorticoids have an overall catabolic or anabolic effect
catabolic
how does adipose tissue change with clucocorticoids
adipose redistributes from limbs to trunk
how is fat affected directly and indirectly with glucocorticoids
fat metabolism so higher circulating fatty acids and glycerol, increased circulating insulin, promotes fat deposition
what do glucocorticoids do to arachionic acid and how
they inhibit it because they inhibit phospholipase A2
what are 3 main targets of glucocorticoid mediated inflammation
arachidonic acid
prostanoid
COX2 (not antagonist!)
how do glucocorticoids affect prostanoid synthesis
inhibit it
because less arachidonic acid
what is the role of COX2
early step of metabolism of arachidonic acid to various prostanoids
how do glucocorticoids regulate COX2
suppress transcription of the COX2 gene
they DO NOT DIRECTLY ANTAGONIST OR INHIBIT COX2 ACTIVITY
it binds to a glucocorticoid receptor which causes a decrease in transcription
what is annexin A-1
anti-inflammatory protein
how does annexin A-1 do its thing (2 ways)
anti-inflammatory by
1-directly effects on leukocytes to inhibit inflammation
2-suppress phospholipase A2
what are the annexin repeats proteins
lipocortins/annexins
what macromolecule is lipocortin
protein
how does lipocortin affect phospholipase A2?
inhibits
how does glucocorticoids affect annexin A-1 pathway
glucocorticoids promotes annexin A-1 which inhibits PLA2
what is addisons disease caused by
chronic adrenocortical insufficiency
low production of glucocorticoids and often mineralocorticoids too
how can you treat addisons disease
with glucocorticoids/mineralocorticoids supplementation (hydrocortisone)
what is cushings syndrome caused by
adrenal overactivity leading to excess cortisol
what can cause cushings disease
tumors (adrenal, pit…)
what are symptoms of cushings disease
round face, fat tummy
bone and muscle catabolism
what kind of things can glucocorticoids be used for
anti-inflammatory, allergic, pain, asthma, GI, organ transplants (immunosuppression to avoid rejection)
what causes addison-LIKE symptoms
administration of glucocorticoids creating negative of CRH and ACTH
what are the side effects of addison-LIKE symptoms
hypoglycemia, hyponatremia (sodium), hyperkalemia(potassium), low bp
why do you need to taper off glucocorticoids
addison-LIKE symptoms
what happens if you use glucocorticoids for a long time
cushingOID
what are the effects of cushingOID
hyperglycemia, high bp, low immune, muscle and bone wasting
what are the two main receptors with different affinities for corticosteroids
glucocorticoid receptor and mineralocorticoid receptor
what does 11beta-hydroxysteroid dehydrogenase type 2 do
inactivates cortisol (alcohol into ketone)
