PH1124 - corticosteroids

Question 1

what are the two steroids synthesized within the adrenal cortex? (2)

Answer 1

• corticosteroids

- androgens

Question 2

what are the two types of corticosteroids? (2)

Answer 2

• glucocorticoids (cortisol)

- mineralocorticoids (aldosterone)

Question 3

what are synthesized in the adrenal medulla?

Answer 3

• catecholamines (noradrenaline and adrenaline)

Question 4

what are the layers of the adrenal gland? (outside to inside) (3)

Answer 4

• zona glomerulosa
• zona fasiculata
• zona reticularis
  (adrenal medulla)

Question 5

what is the role of the zona reticularis?

Answer 5

• secretes glucocorticoids and some sex steroids

Question 6

what is the role of the zona fasiculata?

Answer 6

• widest region that secretes glucocorticoids and some sex steroids

Question 7

what is the role of the zona glomerulosa?

Answer 7

• secrete aldosterone (lacks 17-α-hydroxylase)

Question 8

what are the two pathways of corticosteroid synthesis? (2)

Answer 8

• glucocorticoid pathway (17-hydroxylated corticosteroids)

- mineralocorticoid pathway (17-deoxycorticosteroids)

Question 9

what is the structure of corticosteroids? (3)

Answer 9

• 21 carbon skeleton
• cyclohexane rings A, B and C in ‘chair’ conformation
• cyclopentane ring D

Question 10

what is the synthesis of corticosteroids like in the adrenal cortex? (2)

Answer 10

• only produces steroids as required

- produces sufficient steroids for only a few minutes secretion

Question 11

what stimulates the transport of cholesterol into cells?

Answer 11

• adrenocorticotrophin

Question 12

what is cholesterol transported by in the blood?

Answer 12

• LDL (low density lipoprotein)

Question 13

why is cholesterol important in the synthesis of corticosteroids?

Answer 13

• it is an important precursor when corticosteroid production is stimulated

Question 14

where does cholesterol come from? (3)

Answer 14

• 60-80% comes from your blood
• stored in the adrenal cortex
• made in cells from acetate and acetylcoenzyme A

Question 15

how is cortisol transported in the blood? (2)

Answer 15

• 90% corticosteroid-binding proteins by transcortin and albumin (majority is bound to transcortin)
• 10% free plasma glucocorticoids are biologically active

Question 16

what are the differences in capacity and affinity for the corticosteroid-binding proteins? (2)

Answer 16

• transcortin has a low capacity but high affinity

- albumin has a high capacity but low affinity

Question 17

how are cortisol, corticosterone and aldosterone metabolised and excreted? (4)

Answer 17

• metabolised in the liver
• reduction of 4,5 double bond and the C3 and C20 keto groups
• resultant derivatives conjugated with glucuronic acid or sulphate at C3 hydroxyl group
• excretion in urine

Question 18

what is the regulation of corticosteroid biosynthesis?

Answer 18

• glucocorticoids (in ZF and ZR) cause negative feedback loop causing the anterior pituitary to stop producing ACTH
• the glucocorticoids stop the hypothalamus releasing CRH which also inhibits the production of the glucocorticoids
• the release of ACTH also causes a short negative feedback loop to the hypothalamus to stop the production of CRH

Question 19

what does CRH stand for?

Answer 19

• corticotropin releasing hormone

Question 20

what is CRH?

Answer 20

• causes the anterior pituitary gland to release more ACTH which causes the release of glucocorticoids

Question 21

where is CRH released from and when?

Answer 21

• hypothalamus
• in response to emotional or traumatic stress and the sleep-wake cycle
• release potentiated by vasopressin, oxytocin, adrenaline and cytokines

Question 22

what does CRH act on?

Answer 22

pituitary corticotroph cells

Question 23

what is ACTH?

Answer 23

• adrenocorticotropic hormone

Question 24

what is the release of ACTH regulated by? (2)

Answer 24

• CRH

- glucocorticoids

Question 25

when is ACTH released?

Answer 25

- response to the sleep-wake cycle, stress, psychiatric disturbances, neurotransmitters and peptides

Question 26

what is the secretion of ACTH stimulated by?

Answer 26

- vasopressin

Question 27

what is diurnal variation? (3)

Answer 27

- natural rhythm for the release of CTH and glucocorticoids - adapts of changes in sleep-wake patterns - rhythm controlled by CRH

Question 28

what are steroid receptors?

Answer 28

- located inside the cell (intracellular) and belong to a gene superfamily of nuclear recepotrs - they interact with nuclear DNA to modulate transcription of specific genes

Question 29

what are the steroid receptors found in the cytoplasm? (2)

Answer 29

- glucocorticoids | - mineralocorticoids

Question 30

what are the steroid receptors found in the nucleus? (3)

Answer 30

- androgen - oestrogen - progesterone

Question 31

what is the molecular mechanism of the action of steroids? (3)

Answer 31

- steroids enter the cytoplasm of the cell to bind to a receptor to make a substrate receptor complex - two of the complexes form to make a dimer - this enters the nucleus of the cell and can either up/down regulate the transcription of a gene by the zinc fingers it contains

Question 32

what are the physiological actions of corticosteroids? (7)

Answer 32

- carbohydrate and protein metabolism - fat metabolism - central nervous system effects - effects on bone - mineralocorticoid effects - permissive effects - anti-inflammatory and immunosupressive effects

Question 33

what is the role of corticosteroids in carbohydrate and protein metabolism? (2)

Answer 33

- they antagonise the action of insulin on glucose uptake increasing blood glucose - increase protein breakdown and reduce protein synthesis

Question 34

what would happen to an individual is there were no corticosteroids present?

Answer 34

- if subjected to a shortage of food or extensive exercise they may have hypoglycaemic episodes

Question 35

what would prolonged high doses of corticosteroids cause to an individual?

Answer 35

- hyperglycaemia, wasting of muscle with thinning of capillary walls and loss of the bone matrix

Question 36

how do corticosteroids control fat metabolism?

Answer 36

- they stimulate fat breakdown (lipolysis) and inhibit fat synthesis

Question 37

what do high levels of corticosteroids do to body fat?

Answer 37

- causes redistribution of body fat to the neck shoulders and cheeks with loss of fat from the limbs

Question 38

how do corticosteroids affect the central nervous system? (2)

Answer 38

- involved in the neuronal development in the foetal and neonatal brain - development of the CRH-ACTH axis

Question 39

how do corticosteroids effect bone? (2)

Answer 39

- leads to a net decrease in plasma calcium as it is regulated by calcium metabolism - prolonged doses of glucocorticoid steroids leads to osteoporosis

Question 40

what are the mineralocorticoid effects from corticosteroids?

Answer 40

- increased Na+ reabsorption in exchange for K+ excretion | - increased water retention

Question 41

what are the permissive effects of corticosteroids? (2)

Answer 41

- allow other hormones to exert effects | - helps the body to maintain its temperature and respond to stress

Question 42

what leads to increased cortisol?

Answer 42

- stress

Question 43

how does stress protection work?

Answer 43

- prevents stress-induced defense reactions from getting out of control

Question 44

what are the some of the anti-inflammatory effects caused by corticosteroids? (4)

Answer 44

- decreased vasodilation and fluid exudation by direct vasoconstriction on small blood vessels - decreases fibroblast function so less chronic inflammation - decrease generation of pro-inflammatory mediators and increases the production of anti-inflammatory mediator - stabilises mast cells and lysosomal membranes

Question 45

how does corticosteroids cause immunosuppressive effects? (5)

Answer 45

- decreases the action of T helper cells and reduce clonal proliferation of T cells due to the decreases interleukin production - reduce the numbers of circulating T and B lymphocytes and antibody production - impairs recognition responses in antigen presentation - reduces numbers of toxic radicals produced by macrophages - reduces phagocytic activity of macrophages

Question 46

what happens at the cellular site of action of corticosteroids? (4)

Answer 46

- antigen recognition - stimulation of IL-1 - expression of IL-2 and other cytokines - proliferation and differentiation

Question 47

what controls the secretion of aldosterone?

Answer 47

- controlled mainly by the renin-angiotensin system but hyperkalaemia and ACTH increase release

Question 48

where are the aldosterone receptors found?

Answer 48

- distal and convoluted tubules and collecting duct in the kidney, bladder, colon, sweat and salivary glands

Question 49

what is the main action of aldosterone?

Answer 49

- retain Na+ and lose K+ therefore water is retained because it follows Na+

Question 50

what is the mechanism of action of aldosterone? (3)

Answer 50

- increased production of the Na+ transporter in luminal membrane - pumps Na+ out of the luminal fluid into the tubular cells - increases Na+/K+ ATPase pump to pump Na+ out of tubular cells into the plasma increasing the blood volume

Question 51

what is cushings disease/syndrome?

Answer 51

- increased ACTH (adrenocorticotropic hormone) causes increased cortisol

Question 52

what are the symptoms of cushings disease? (6)

Answer 52

- muscle weakness and wasting - easily bruised - redistribution of body fat - prominent abdomen - diabetes - high levels of plasma and urine cortisol