Steroids

Question 1

steroid hormones that function to regulate inflammation/metaboolism

Answer 1

glucocorticoids

Question 2

steroid hormones that function to regulate salt homeostasis

Answer 2

mineralcorticoids

Question 3

where are corticosteroids produced?

Answer 3

adrenal cortex

Question 4

what zone of the adrenal cortex makes glucocorticoids?

Answer 4

zona fasiculata

Question 5

what are steroids derived from?

Answer 5

cholesterol

Question 6

hypothalmic-pituitary axis

Answer 6

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

Question 7

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

Answer 7

ACTH

Question 8

negate feedback in corticosteroid production

Answer 8

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

Question 9

roles of glucocorticoids

Answer 9

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

Question 10

metabolic role of glucocorticoids

Answer 10

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

Question 11

catabolic role of glucocorticoids

Answer 11

protein, bone, etc

Question 12

immunosuppresive role of glucocorticoids

Answer 12

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

Question 13

anti-inflammatory role of glucocorticoids

Answer 13

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

Question 14

four functional domains of glucocorticoid receptor

Answer 14

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

Question 15

LBD of GR

Answer 15

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

Question 16

DBD of GR

Answer 16

binds to specific DNA sequence called GRE on target gene

Question 17

AF2 of GR

Answer 17

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

Question 18

AF1 of GR

Answer 18

N terminal end, constitutively interacts with transcription machinery

Question 19

mechanism of glucocorticoid action

Answer 19

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

Question 20

lipocortin

Answer 20

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

Question 21

IL6/8

Answer 21

proteins whose expression is inhibited by glucocorticoids.

Question 22

property of synthetic steroids

Answer 22

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

Question 23

when would we treat someone with physiologic doses of corticosteroids?

Answer 23

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

Question 24

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

Answer 24

for an anti-inflammatory or immunosuppresive effect

Question 25

mechanism of anti-inflammatory role of corticosteroids

Answer 25

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

Question 26

toxicity of glucocorticoids on hypothalamic pituitary axis

Answer 26

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

Question 27

acute adrenal insufficiency

Answer 27

Addisonian crisis

Question 28

side effects of glucocorticoids

Answer 28

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