adrenal glands

Question 1

what is cortisol for?

Answer 1

o Stress Response
o Raises Blood Sugar
o Protein/Fat Metabolism
o anti-inflammatory

Question 2

what is aldosterone for?

Answer 2

o Increases serum [Na+]

o Raises blood pressure

Question 3

what are androgen precursors for?

Answer 3

maturation and development

Question 4

where are adrenal glands situated?

Answer 4

Adrenal glands are not part of the kidney they sit on top of the kidney. It is possible to lose one and the other one would be able to support physiological function.

Question 5

what are the three parts of the adrenal gland?

Answer 5

Three parts to the adrenal gland – the outer capsule is where the blood supply is. The cortex is what is produces and stores the steroids and the medulla is where the catecholamines are produced.
Two very discrete tissues – come from different places.

Question 6

what is the cortex called?

Answer 6

glomerulus and this is where aldosterone is produced.

Question 7

what is the middle part of the cortex called?

Answer 7

zona Fasciculata and it produces cortisol

Question 8

what is the end part of the cortex closest to medulla called?

Answer 8

Zona Reticularis and this produces Adrenal Androgens”/ “Androstenediones”

Question 9

where are steroid exocytosised?

Answer 9

secretary granules

Question 10

what are steroids synthesised from?

Answer 10

cholesterol is the primary precursor molecule

Question 11

what is a conserved pathways?

Answer 11

not that many different enzymes but the process of the enzyme.
• Having enzymes in different parts means there is a safety check to make sure you are making the right amount throughout the process.

Question 12

what is the rate limiting step in steriodogenesis?

Answer 12

cholesterol to pregnenolone

Question 13

what do glucocorticoids do?

Answer 13

o Metabolic effects -glucose like effect
o Anti-inflammatory
o Immunosuppressive

Question 14

what are mineralcorticoids for?

Answer 14

water and electrolyte balance

Question 15

what is the mechanims of action of corticosteroids?

Answer 15

• Produced and released into adrenal cortex until they bind.
• Corticosteroid binding globulin (transcortin) binds 90% of cortisol and 60% of aldosterone.
• Transcortin does not bind synthetic steroids. – endogenous binding protein, powerful carrying protein. Doesn’t bind synthetic as the shape is different in key regions compared to that of the endogenous proteins.
• Albumin binds synthetic and natural steroids
• When they get to there target site their main actions involve changes in gene transcription & translation.
• Altering the synthesis of specific proteins in target cells.
• Aldosterone can have immediate effect on cells as they have receptors on there surface
• Steroids change protein turnover (slower)

Question 16

what controls glucocorticoid release?

Answer 16

stressful event will cause the hypothalamus to become activated. Once it is activated and stimulated in response to signal it then release corticotropin releasing hormone which stimulates release of ACTH and this then reaches circulation to allow the synthesis of cortisol to begin – this has important effects on the body. All increase the bodies metabolic status or provide us with protection.

Question 17

what is the mechanism of action of mineralcorticoids?

Answer 17

• MC receptors have a limited tissue distribution
• MCs cause Na + -uptake leading to fluid resorption, and K+ loss
• Spironolactone acts as competitive inhibitor of MC receptors: diuretic & antihypertensive
• Aldosterone released is caused by increase in Angiotension II
• When aldosterone is released it increase salt retention and increases blood vessel constriction and causes blood pressure to increase.

Question 18

what are the varying half lifes of the synthetic steroids?

Answer 18

o Short-acting, t1/2 8-12h (e.g. hydrocortisone, fludrocortisone)
o Intermediate, t1/2 12-36h (e.g. prednisolone)
o Long-acting, t1/2 36-72h (dexamethasone, betamethasone)

Question 19

what are the different split activities of synthetic steroids?

Answer 19

o Mixed GC/MC activity – e.g. prednisolone, (prednisone)
o Pure GC – e.g. dexamethasone, betamethasone, beclomethasone,
o Mainly MC – e.g. fludrocortisone

Question 20

what are the symptoms of addisons disease?

Answer 20

• appetite lose / untentional weight loss
• discolouration of skin
• dehydration
• increased thirst
• salt, soy sauce, liqourice cravings
• oligomenorrhoea
• no energy or motivatio
• sore/painful, weak muscles

Question 21

what is addisons disease?

Answer 21

Addisons is a problem with adrenal gland insufficiency and you need to be able to replace the lost hormones. As the patient cannot make its own endogenous steroids.

Question 22

what is the treatment of addisons disease?

Answer 22

• Hydrocortisone (GC) with or without fludrocortisone (MC)

* Limited side-effects as plasma levels mimic natural situation

Question 23

how do steroid restore endocrine control congential adrenal hyperplasia?

Answer 23

• Fault in steroidogenesis pathway
• Over-production of androgens
• Limited / no cortisol negative feedback
• ACTH output is raised
• Synthetic steroids are used to recover the missing feedback e.g. dexamethasone, betamethasone have few side effects as plasma levels mimic natural situation
• As they aren’t producing cortisol they cannot switch of the hormone production so there is still a physical drive but there is no physiological function to switch them off, so production continues.

Question 24

how are steroids used as anti-inflammatory?

Answer 24

o Reduce mediators of inflammation and immune responses inc. prostaglandin, cytokines, NO, IgG, etc
o Applications: asthma, eczema, arthritis, psoriasis, allergic rashes, itching …. .etc
o Agents: hydrocortisone, prednisolone, beclomethasone, dexamethasone, budesonide, etc

Question 25

when would you use steroidgenesis as a drug target?

Answer 25

• inhibitor of steroid synthesis
• selective inhibition
• ACTH mimic