corticosteroids and steroid receptors - 1 Flashcards
what are the two major classes of corticosteroids
glucocorticoids and mineralocorticoids
which is the main endogenous glucocorticoid
cortisol
what are 2 main functions for glucocorticoids
metabolism
anti-inflammatory
which is the main endogenous mineralocorticoid
aldosterone
what are 2 main functions for aldosterone
water and electrolyte balane
what controls the secretion of cortisol
hypothalamic-pituitary-adrenal HPA axis
what is a diurnal rhythm
a pattern of activity based upon a 24-hour cycle, in which there are regular light and dark periods
when does cortisol peak in humans
why
early morning (diurnal rhythm)
what are 2 main stimulus for cortisol secretion
physical and psychological stressors
what are 4 physical stressors for cortisol secretion
heat
cold
injuries
infections
what are 3 psychological stressors for cortisol secretion
money
work
relationships
what kind of feedback does cortisol do on the hypothalamus
negative
what kind of feedback does cortisol do on the pituitary gland
negative
where is cortisol released from
adrenal cortex
what causes cortisol release from the adrenal cortex
ACTH activation
where is ACTH release
anterior pituitary
what negatively inhibits the anterior pituitary from releasing ACTH
cortisol
what are the factors released by the hypothamaus that causes ACTH release from the ant pit
CRH and AVP
what is CRH and AVP
the factors released by the hypothamaus that causes ACTH release from the ant pit
does CRH or AVP play a bigger role in the stress response
CRH
what 2 things cause the release of ACTH from the ant pit (and where do they come from)
CRH AVP from the hypothalamus
where is the site of synthesis of cortisol (specific)
zona fasciculate of adrenal cortex
what is the starting substance of cortisol
cholesterol
what G protein does ACTH act through
Gs (adenylate cyclase)
what is the rate limiting step of cortisol synthesis
conversion of cholesterol to pregnenolone
how is cortisol relased from the adrenal cortex
diffusion across plasma
why can cortisol just diffuse out of the adrenal cortex
because its highly lipid soluble (made from cholesterol)
what 2 things can plasma cortisol bind to
albumin and corticosteroid-binding globulin (CBG)
what does CBG stand for
corticosteroid-binding globulin
what does corticosteroid-binding globulin do
binds only to natural cortisosteroids
what does albumin do
binds to both natural and synthetic cortisol
what 2 things cause an increase in CBG (corticosteroid-binding globulin) levels
estrogen
hyperthyroiddism
what 2 things cause a decrease in CBG (corticosteroid-binding globulin) levels
hypothyroidism
protein deficiency
what happens with cortisol with high estrogen levels and why
less plasma cortisol because more is bound by CBG
what happens with cortisol with hyperthyroidism and why
less plasma cortisol because more is bound by CBG
what happens with cortisol with hypothyroidism and why
more plasma cortisol because less is bound by CBG
what happens with cortisol with protein deficiency and why
more plasma cortisol because less is bound by CBG
what binds to both natural and synthetic cortisol
albumin
what binds to only natural cortisol
CBG (corticosteroid-binding globulin)
what is the overall effect of glucocorticoids on sugar levels
increase sugar levels in blood so that theres adequate supply of glucose to the brain
what do glucocorticoids do to glucose uptake in skeletal muscle
decreases
what do glucocorticoids do to glucose use in skeletal muscle
decrease
what do glucocorticoids do to gluconeogenesis
increase
what do glucocorticoids do to insulin
increases secretion
why do glucocorticoids increase insulin secretion
because there is a rise in plasma glucose
what do glucocorticoids do to protein breakdown
increase
what do glucocorticoids do to protein synthesis
decrease
where does glucocorticoids have a catabolic effect
lymphoid, connective tissue, muscle, skin and bone
what do glucocorticoids do to lipolysis
increase
what do glucocorticoids do to lipogenesis and why
increase due to insulin secretion
what does insulin do to lipogenesis
increase
what is the overall effect of glucocorticoids on fat
increases fat deposition
if cortisol causes lipolysis, why does fat deposition occur
cortisol causes lipolysis
but insulin causes lipogenesis
so in this case lipogenesis wins
what do glucocorticoids do to # of immune cells
decreases
what do glucocorticoids do to macrophage functions
inhibits
what do glucocorticoids do to fibroblast functinos
decreases
what do glucocorticoids do to cytokine production and actions
decrease
what do glucocorticoids do to IgG production
decrease
what do glucocorticoids do to blood vessels
decrease in vasodilation
what do glucocorticoids do to histamine release from mast cells and basophils
decrease
what do glucocorticoids do to CRH and ACTH secretion
inhibition via negative feedback
what does ACTH do to adrenal cortex
maintenance, including making sure theres no atrophy
what do glucocorticoids do to adrenal cortex
how
causes atrophy
reduce ACTH levels so a decrease in size of adrenal cortex
what do glucocorticoids do to blood vessel size
vasoconstriction
what do glucocorticoids do to BP
increase
what do glucocorticoids do to vascular responsiveness (and to what)
increased responsiveness to angiotensin2 NA A
what do glucocorticoids do to Ca++
negative Ca++ balance
- decreased Ca++ uptake via GI
- increased kidney Ca++ excretion
what do glucocorticoids do to musculoskeletal system
decreased osteoblast activities, increased osteoclast activities
what do glucocorticoids do to behaviour initially
insomnia, euphoria
what do glucocorticoids do to subsequently (not initially)
depression
what is excessive cortisol linked to
major depressive disorders
what are 5 symptoms of decreased cortisol levels
- muscle weakness
- fatigue
- weight loss
- hypotension
- fasting hypoglycemia
what are 3 symptoms of decreased aldosterone levels
dehydration
hyponatremia
hyperkalemia
what can cause acute adrenocortical insufficiency
abrubt withdrawal of exogenous glucocorticoid after prolonged therapy
how long can adrenocortical insufficiency from exogenous glucocorticoid recovery take
several months
what is addisons disease
chronic adrenocortical insufficiency
what can cause addisons disease
autoimmune, infection, cancer, congenital unresponsiveness to ACTH
why does fasting hypoglycemia happen with adrenocortical insufficiency
cortisol usually stops sugar uptake into cells, so with less cortisol, there will be low plasma sugar
what causes congenital adrenal hyperplasia
lack of 21β-hydroxylase
what happens in congenital adrenal hyperplasia (what is affected)
- reduction in cortisol and aldosterone synthesis
- increased ACTH (less -ve feedback)
- increased androgens and estrogen
what happens to cortisol with congenital adrenal hyperplasia
levels reduce
what happens to aldosterone with congenital adrenal hyperplasia
less synthesis
what happens to ACTH with congenital adrenal hyperplasia and why
more because less negative feedback
what happens to androgen with congenital adrenal hyperplasia + why
increase because more androstenedione
what happens to estrogen with congenital adrenal hyperplasia + why
increase because more androstenedione
which pathway is favorted with 21β-hydroxylase defect and why
sex steroid pathway because 21β-hydroxylase works mostly in the mineralocorticoid and glucocorticoid pathways
what metabolite becomes excess with 21β-hydroxylase defect
androstenedione
what is the main thing that 21β-hydroxylase metabolizes
progesterone
what characterises cushings disease
high plasma level of cortisol
what causes cushings disease (3)
pituitary adenoma (tumor)
nodular hyperplasia of adrenal gland
ectopic production of ACTH by other tumor (not in pit)
what is required after surgical removal in cushings disease
glucocorticoid replacement
in cushings disease, what would an adrenal or pituitary gland tumor release
adrenal-cortisol
Pituitary-ACTH
what is the diagnostic test called for cushings disease
dexamethasone suppression test
how do you do the dexamethasone suppression test
administer dexamethasone at night, measure plasma cortisol level
what would indicate a cortisol producing tumor with the dexamethasone suppression test
high cortisol and low ACTH
what is dexamethasone
a synthetic cortisol
what would indicate a ACTH producing tumor with the dexamethasone suppression test
high cortisol and high ACTH
what would high cortisol and low ACTH mean with a dexamethasone suppression test
cortisol producing tumor
what would high cortisol and high ACTH mean with a dexamethasone suppression test
ACTH producing tumor
where are 2 places that an ACTH producing tumor could be
in pituitary or lungs
where is 1 place that a CORTISOL producing tumor could be
in adrenal glands
why would there be high cortisol and low ACTH with a dexamethasone suppression test in a CORTISOL producing tumor
because adrenal tumor makes cortisol so theres negative feedback so low ACTH
what are 2 clinical uses for glucocorticoids
diagnostic test (cushings disease ) or lung maturation
what does cortisol do to lungs
regulates lung maturation in fetus
why can cortisol be used therapeutically for lungs (and for who)
immature lung development in fetuses because cortisol regulates lung maturation in fetus
what can cause immature lung development in fetuses
low maternal cortisol or early birth
what can cortisol administration do to infants with resp issues
reduce incidence of respiratory distress
