Glucocorticoids

Question 1

two classes of corticosteroids

Answer 1

glucocorticoids (eg cortisol)

mineralocorticoids (eg aldosterone)

Question 2

where are corticosteroids synthesised

Answer 2

in the adrenal cortex

Question 3

what do glucocorticoids do

Answer 3

regulate carbohydrate and protein metabolism.

have anti-inflammatory effects

Question 4

what do mineralocorticoids do

Answer 4

regulate electrolyte and water balance and thus control volume regulation.

Question 5

how is cortisol released

Answer 5

hypothalamus releases CRH into median eminence of the pituitary gland.
CRH travels in portal circulation -> ant pituitary .’. release of ACTH into systemic circulation -> adrenal cortex where stimulates inc. production and release of cortisol from zona fasciculata

Question 6

what releases acth

Answer 6

corticotrophs of ant. pituitary

in response to CRH

Question 7

how is cortisol release regulated

Answer 7

in -ve feedback manner

cortisol release can turn down secretion of ACTH and CRH to control its levels

Question 8

how is aldosterone released

Answer 8

dec. renal perfusion, symp stimulation or low Na+ can trigger juxtoglomerular cells to release renin.
conversion of angiotensinogen to angiotensin I.
ACE converts ang 1 -> ang 2 in the lung
ang 2 has various effects inc. stimulatulating release of aldosterone.
Low Na+ in blood can also directly stimulate aldosterone release.

Question 9

effect of aldosterone

Answer 9

inc reabsorption of Na+ in teh renal tubule .’. inc. reabsorption of water .’. inc bv and inc bp

Question 10

how is aldosterone release controlled

Answer 10

inc reabsorption of Na+ in teh renal tubule .’. inc. reabsorption of water .’. inc bv/bp .’. can turn down release of renin
also inhibitory pathway of ANP. if BV too high = high bp = atria overstretch .’. release ANP which antagonises RAAS system .’. reduce aldosterone release

Question 11

what are metabolic effects of glucocorticoids

Answer 11

inc breakdown of protein and fat (can lead to muscle wasting)
decrease glucose usage
inc gluconeogenesis in liver (conserve glucose)
.’. tendency of hyperglycemia and inc glycogen storage

Question 12

effects of glucocorticoids on cvs

Answer 12

important at maintaining vascular integrity
decrease microvascular permeability and decreased vasdilatation
(bc are anti-inflammatory)

Question 13

effects of glucocorticoids as anti-inflammatory

Answer 13

decrease microvascular fluid exudation (.’. less influx of cells to areas of inflammation)

• decrease expression of inflammatory mediators and cytokines
• decrease expression of COX
• decrease function of inflammatory mediator cells
  inhibit cell migration and mediator release, reduce clonal explansion of t and bcells, reduce chronic inflammatory process

Question 14

how do glucocorticoids get into cells

Answer 14

are steroids .’. passive diffusion through membrane and enter cytosol

Question 15

what receptor do glucocorticoids work at

Answer 15

GCr which is a ligand activated nuclear transcription factor

Question 16

mechanism of glucocorticoids

Answer 16

diffuse into cytosol, bind to GCr. receptor dissociates from HSP complex = now an activated transcription factor .’. enters nucleus .’. binds to the promoter of any gene containing glucocorticoid response element (GRE), and upregulate or downregulate the expression of that gene

Question 17

why is body so affected by glucocorticoids

Answer 17

about 1% of entire genome is steroid sensitive .’. affects transcription .’. affected a lot of genes

Question 18

roles of glucocorticoid-GCR complex

Answer 18

able to up regulate/downregulate expression of genes

able to prevent gene activation by other transcription factors

Question 19

mechanism of COX inhibition by glucocorticoids

Answer 19

glucocorticoid-GCR complex able to prevent gene activation by other transcription factors
transcription factors AP1/NFkB involved in upregulating COX2 and immune cells so by blocking these we turn down inflammation

Question 20

why are glucocorticoids such potent anti-inflammatory agents

Answer 20

1 - inc expression of anti-inflammation (e.g. by inc lipocortin .’. decr. arachidonic acid and eicosanoids
2 - dear. production of inflammatory mediators (e.g. reduce cytokine production .’. dec activity of cox2)

Question 21

treatment for adrenal insufficiency or failure

Answer 21

giving both glucocorticoid and mineralocorticoid drugs due to low levels of these circulating hormones.

Question 22

why do we give glucocorticoids to transplant patients

Answer 22

to inhibit rejection of graft tissue by host in tissue transplantation

Question 23

clinical glucocorticoids include

Answer 23

hydrocortisone, prednisolone, dexamethasone, betamethasone and beclomethasone.

Question 24

mechanism of glucocorticoids in anti-inflammatory effects

Answer 24

inhibit PLA2 (phospholipase A2) synthesis .’. stop formation of AA .’.stop expression of COX =completely shut down eicosanoid synthesis

Question 25

where are mineralocorticoids produced

Answer 25

by zona glomerulosa of adrenal cortex

Question 26

what controls secretion of aldosterone

Answer 26

dependent on RAAS and ACTH

Question 27

mechanism of action of aldosterone in increasing blood vol

Answer 27

aldosterone enters tubular cells of kidney. binds to receptor (ligand activated transcription factor) .’. unregulates luminal membrane ENaC channels and basolateral 3Na+/2K+ ATPase .’. get an Na+ gradient (e/ inc Na into plasma/circulation) with water following.’. bv increases
BUT increases loss of K+ and H+

Question 28

where are mineralocorticoid receptors found

Answer 28

kidney, colon and bladder. These are important in volume control.

Question 29

what happens if you have a lack of aldosterone

Answer 29

salt wasting crisis =losing lots of Na+

can lead to hypotension bc low bv

Question 30

in what conditions would we administer aldosterone clinically

Answer 30

adrenal insufficiency
electrolyte disorders
orthostatic hypotension

Question 31

side effects of corticosteroids

Answer 31

euphoria, lipodystrophy, inc abdominal fat, moon face, buffalo hump, opportunistic infection, osteoporosis, gastric ulceration, growth suppression

Question 32

what is lipodystrophy

Answer 32

disproportionate fat accumulation and wasting