Glucocorticoids Flashcards
(41 cards)
where is cortisol produced?
adrenal cortex- fasciulate and reticularis
which is produced more: cortisol or aldo?
cortisol 100x more than aldo
what is the blood concentration of cortisol? how does it travel
.4 uM- 96% bound to corticosteroid binding globulin
free cortisol is biologically active
what is the defining chemical feature of cortisol?
OH at 11th position
where is aldosterone produced
glomerulosa (outer most cortex)
what is the precursor for all adrenocortical hormones?
cholesterol
what is the first step in converting the adrenocortical hormone precursor into either aldo or cortisol?
cholesterol desmolase (p450) converts it into pregnenolone
what are the actions of 21B-hydroxylase
converts 17-hydroxyprogesterone towards cortisol
converts progesterone towards aldo
also a p450 enzyme
21B-hydroxylase deficiency
results in excess androgens and accelerated development of secondary sexual characteristics.
w/o negative feedback of cortisol, increased ACTH secretion
where does cortisol feedback?
negative on pit (inhibit ATCH) and hypo (inhibit CRH)
congenital adrenal hyperplasia
ACTH acts as a growth factor on the adrenal gland. in deficiencies such as 21B-hydroxylase, w/o negative feedback from cortisol, unregulated ACTH causes excess adrenal growth
how does ACTH exert its effects on the adrenal glands
ACTH receptor is MC2R- Gs protein that increases cAMP, which releases IP3 and DAG to activate PKC, which increases steroid response immediately, and a tropic growth effect over the long term
how does cortisol exert its effects?
receptor- GR- cytoplasmic receptor
cortisol diffuses through cell and binds receptor, causing it to translocate into nucleus, altering protein transcription
where are cortisol receptors found?
entire body
what is the timeline of cortisol effects?
slow- related to changes in transcription
what are the effects of cortisol on the body?
- raises blood sugar by stimulating gluconeogensis and glycogenolysis
- increases circulating lipids via lipolysis
- inhibits peripheral glucose uptake
- redistribution of body fat to trunk
- increases effects of vascular pressors by increasing AVP receptors
- initiate muscle breakdown for protein
- anti-inflammatory and immunosuppressive actions (decrease in cytokine production)
- decreases bone mass and impairs wound healing by increasing osteoclast number and decreasing fibroblast protein synthesis
-CNS effects-
insomnia, hyperactivity, increase appetite, impairs memory
how are cortisols effects related to insulin?
they antagonize each other
what is the main stimulus for cortisol release?
stress- caused by trauma, emotional situations, and changes in blood sugar or blood volume
what are the differences between primary, secondary, and tertiary adrenal deficiencies
1 d/t destruction of adrenal cortex (Addisons)
2 inadequate ACTH secretions
3 inadequate CRH secretion
why is hyperpigmentation seen in Addisons
MSH comes from the same precursor as ACTH, which is continuously stimulated b/c of a lack of cortisol
what are the symptoms of Addisons
hyperpigmentation weakness/fatigue hypotension weight loss naseau/vomitting loss of appetite fasting hypoglycemia muscle/joint pain
what is Cushing syndrome?
hypercortisolism- 2 types
ACTH dependent- ACTH or CRH hypersecretion
ACTH independent- adrenal tumor or medicated
what are the symptoms of Cushings syndrome?
trunal obesity moon face buffalo hump abdominal striae osteoporosis hypertension brusing poor wound healing glucose intolerance/diabetes psychosis infections hirusitism
what is the major minerlocorticoids?
aldosterone
