GV6: Inducible Transcription Factors

Question 1

where are endgenous corticoids found

Answer 1

released from adrenal cortex

Question 2

what are mineralocorticoids (aldosterone)

Answer 2

affect water and electrolyte balance

Question 3

what are glucocorticoids (hydrocortisone, corticosterone)

Answer 3

affect carbohydrate and protein metabolism

anti-inflammatory and immunosuppressive effects

Question 4

what are the metabolic side effects of steroids

Answer 4

osteoporosis, diabetes, mineralocortocoid effects

Question 5

how do steroids cause osteoporosis

Answer 5

decrease in collagen synthesis, osteoblast function, calcium absorption by inhibition of vitD action
parathyroid hormone then increases Ca resorption from bone

Question 6

how do steroids cause diabetogenisis

Answer 6

due to decrease in glucose uptake and utilisation and increase in gluconeogenesis plus increased apetite which can lead to obesity

Question 7

how do steroids cause mineralocortocoid effects

Answer 7

Na/H2O retention, hypertension, oedema and cardivascular events

Question 8

what does excessive use of endogenous corticoids cause

Answer 8

cushing’s syndrome

Question 9

how are steroids used as transcription factors

Answer 9

lipophilic hormones
bind intracellular receptors
execute long term effects
regulate gene transcription and mRNA stabalisation
10-100 steroid responsive genes in each cell

Question 10

what is the receptor and function of glucocorticoids

Answer 10

GR receptor

increase blood sugar and anti-inflammatory

Question 11

what is the receptor and function of mineralocorticoids (aldosterone)

Answer 11

MR receptor

maintain water/salt balance

Question 12

what is the receptor and function of testosterone

Answer 12

AR receptor

masculinisation

Question 13

what is the receptor and function of beta-estradiol

Answer 13

ER receptor

feminisation

Question 14

what is the receptor and function of vitamin D

Answer 14

VDR receptor

bone development and calcium metabolism

Question 15

what is the mechanism of action of glucocorticoids

Answer 15

enter cells and bind to cytoplasmic receptors
complex translocates to the nucleus to act as transcription factor
can bind to response elements and activate anti-inflammatory gene transcription
can bind and repress pro-inflammatory gene activation
can interact and inhibit binding of other transcription factors

Question 16

what are the anti-inflammatory effects of steroids

Answer 16

inhibit both early and late stages of inflammatory response
decrease vasodilation and extravasation
inhibit cell activation TH(inhibit IL-2 and clonal expansion)
decrease production of inflammatory mediators
endogenously prevent ‘overshoot’ of immune response

Question 17

how is toxicity of corticosteroids caused

Answer 17

associated with high doses and systemic long-term administration, immunosuppression can increase the risk of infections, impired leukocyte traffic can delay wound healing, suppress HPA axis through feedback inhibition

Question 18

where are steroid response elements located

Answer 18

in enhancers which activate nearby promoters

Question 19

what are steroid response elements

Answer 19

consists of two half-site repeats; half-sites (repeats) separated by 0-4bp; suggests receptors bind as multimers

Question 20

what are the different forms of homodimers

Answer 20

GR, MR, AR, ER, PR

Question 21

what are homodimers

Answer 21

cytoplasmic and nuclear localisation; each subunit of dimer binds one repeat; half sites are inverted repeats (palindromes)

Question 22

what are heterodimers

Answer 22

nuclear location activated when ligand binds; bind direct repeat half-sites; recognition determined by spacing

Question 23

what receptors does RXR form a dimer with

Answer 23

vit D (VDR)
retinoic acid (RAR)
triidothyronine (T3R)