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Flashcards in Steroids Deck (28):
1

steroid hormones that function to regulate inflammation/metaboolism

glucocorticoids

2

steroid hormones that function to regulate salt homeostasis

mineralcorticoids

3

where are corticosteroids produced?

adrenal cortex

4

what zone of the adrenal cortex makes glucocorticoids?

zona fasiculata

5

what are steroids derived from?

cholesterol

6

hypothalmic-pituitary axis

hypothalamus releases chemical stimulators (release hormones) that travel to pituitary gland via portal venous circulation and anterior pituitary then releases additional stimulatory mediators that cause tissues to release hormones

7

what hormone is secreted by the anterior pituitary that stimulates cortisol release?

ACTH

8

negate feedback in corticosteroid production

hypothalamus senses plasma concentration of corticosteroids and down regulates ACTH when it is high. ACTH also has its own negative feedback loop. FINE TUNE REGULATION

9

roles of glucocorticoids

metabolic, catabolic, immunosuppresive, anti-inflammatory, Na homeostasis, behavioral

10

metabolic role of glucocorticoids

gluconeogenesis, lipolysis (hormone sensitive lipase), lipogenesis (insulin)

11

catabolic role of glucocorticoids

protein, bone, etc

12

immunosuppresive role of glucocorticoids

cell mediated immunity (T cell impairment), reduced proliferation of lymphocytes/neutrophils/monocytes

13

anti-inflammatory role of glucocorticoids

inhibition of PLA2, decrease transcription of COX, decrease IL-2,3, decrease pro-inflammatory cytokines

14

four functional domains of glucocorticoid receptor

ligand binding domain (LBD), DNA binding domain (DBD), AF2, AF1

15

LBD of GR

where receptor interacts with chaperone proteins (HSP90/56) and glucocorticoid

16

DBD of GR

binds to specific DNA sequence called GRE on target gene

17

AF2 of GR

C terminal end, interacts with co-activator or suppressor proteins that modulate gene transcription

18

AF1 of GR

N terminal end, constitutively interacts with transcription machinery

19

mechanism of glucocorticoid action

enters cell, binds to GR, allowing it to dissociate from chaperone proteins. Steroid/receptor complex then enters nucleus, binds to GRE and amplifies/suppresses transcription of target gene

20

lipocortin

protein whose expression is unregulated by glucocorticoids. down regulates PLA2, leading to decreased prostanoids

21

IL6/8

proteins whose expression is inhibited by glucocorticoids.

22

property of synthetic steroids

alteration in some portion of chemical structure enhances either gluco or mineral corticoid function.

23

when would we treat someone with physiologic doses of corticosteroids?

during replacement therapy to treat adrenal insufficiency. don't want to throw off the negative feedback loop

24

when would we treat someone with supra physiologic doses of corticosteroids?

for an anti-inflammatory or immunosuppresive effect

25

mechanism of anti-inflammatory role of corticosteroids

decreases t cell production of IFNy, macrophage production of IL1/TNFa, mast cell production of histamine/NO/prostaglandins, suppresses activity/activation of T cells and their cytokine production

26

toxicity of glucocorticoids on hypothalamic pituitary axis

with high doses of glucocorticosteroids, negative feedback turns off hypothalamic induction of ACTH. but sudden withdrawal of therapy can lead to acute adrenal insufficiency

27

acute adrenal insufficiency

Addisonian crisis

28

side effects of glucocorticoids

electrolyte imbalance aka sodium retention causing fluid retention and hypertension. immunosuppresion, myopathy or wasting of proximal muscles, behavioral changes (extra energy, insomnia, psychosis), osteoporosis, hyperglycemia (type 2 diabetes), cataracts, growth retardation