corticosteroids

Question 1

How does glucocorticoids impact inflammation

Answer 1

they reduce inflammation

Question 2

How is glucocorticoids released

Answer 2

pituitary release ACTH which causes release of mineral corticoids (e.g. aldosterone which control K+/Na+)
and causes release of glucocorticoids (suppress immune system, increase protein+carbohydrate metabolism, response to stress)

Question 3

negative feedback of glucocorticoid

Answer 3

-increase in glucocorticoid acts on pituitary to stop ACTH release

Question 4

endogenous vs exogenous glucocorticoid in blood

Answer 4

endogenous- very hydrophobic don’t dissolve in blood so travel bound to plasma protein

exogenous - more soluble travels in blood unbound

Question 5

mechanism of action of glucocorticoid

Answer 5

• steroids pass straight through the membrane as hydrophobic (dissociates from any plasma protein)
• they bind to an intracellular receptor, binding causes heat shock proteins to fall off receptor this leaves receptor active with the zinc fingers exposed (2 zinc fingers on receptor each bind 2 bases)
• the glucorticoid + receptor complex migrate into the nucleus
• the GC - receptor complex has DNA binding domains called zinc fingers
• the tips of the Zinc finger binds to specific base pairs on the glucocorticoid response element of the DNA they look for inverted repeats
• when the zinc fingers bind they will either inhibit or promote mRNA production

Question 6

what happens during intiation of mRNA

Answer 6

-2 receptor complexes bind near same site at the repeats and dimerise this switches on RNA polymerase this promotes the mRNA production of e.g. lipocortins which inhibit A2 so no inflammatory cells formed

Question 7

what happens during inhibition of RNA

Answer 7

-a single receptor binds so there is no dimerisation this can block the production of proteins like collagen which are required for wound healing

Question 8

how steroid dimer receptor acts as a transcription factor

Answer 8

• proximal control elements allows the RNA polymer to bind to promoter region of DNA

-the steroid receptor dimer bound to the (responsive elements of DNA) loop around allows the steroid dimer to make contact with the RNA polymerase
this allows activation of the RNA polymerase to do its job ( in initiators)

if inhibitor the steroid dimer transcription factor will hold RNA polymerase in place stopping it doing its job

Question 9

Other ways glucocorticoids work

Answer 9

glucocorticoid works via other pathways not just via mRNA can work by staying in cytoplasm using kinases this is faster than going in nucleus

Question 10

Glucocorticoid effects on inflammatory mediators

Answer 10

-REDUCES
COX2 - makes prostgladins
iNOS - vasodilation + kill bac
MMP- degrades collagen at Joints
Collagen -used in wound healing 
IL2 and IL6- prime WBC

INCREASES
lipocortin which inhibits phospholipase A2 used to make archandonic acid

Question 11

side effects of glucocorticoids

Answer 11

• decreases fibroblast- reduces wound healing
• decrease in osteoblast- can cause brittle bones
• decreases macrophage sensitivity to cytokines