Glucocorticoids-Cortisol

Question 1

How to remember which steroids are created where in the adrenal cortex?

Answer 1

G: salt
F: sugar
R: sex

Question 2

Where does glucocorticoid get its name?

Answer 2

From raising plasma glucose levels

Question 3

What do glucocorticoids regulate?

Answer 3

Immune
Developmental
Body fluid homeostasis
Metabolism
Arousal and cognition
Decreases cannabinoid CB1 receptor

Question 4

What do glucocorticoids cause when they bind GR?

Answer 4

Regulates epidermal growth factor reducing its activity which in turn reduces creation of arachidonic acid (therefore COX2)

Question 5

Where is the glucocorticoid hormone cortisol formed?

Answer 5

In the zona fasciculata

Question 6

What turns stored cholesterol into free cholesterol in the zona fasciculata?

Answer 6

Cholesterol ester hydrolyase

Question 7

What encodes cholesterol side-chain cleavage enzyme desmolase?

Answer 7

CYP11A1 gene

Question 8

What binds HDL on the adrenal cortex cell membranes?

Answer 8

SRB1 encoded by SCARB1 gene

Question 9

Pathway for how cholesterol is converted to cortisol?

Answer 9

Cholesterol-> Pregnenolone-> Progesterone-> 17-hydroxyprogesterone-> 11-deoxycortisol-> cortisol

Question 10

In the absence of CYP11B1 what pathway is used instead of cholesterol-> cortisol?

Answer 10

Progesterone-> 11-deoxycorticosterone (DOC)-> corticosterone

Question 11

Why is DOC significant?

Answer 11

DOC acts as a weak mineralocorticoid and elevated levels lead to hypertension

Question 12

Key cytochrome P-450 enzyme involved in cortisol synthesis?

Answer 12

17alpha-hydroxylase

Question 13

What triggers synthesis and release of cortisol?

Answer 13

Paraventricular neurons (hypothalamus)

Question 14

What transports cortisol in the blood?

Answer 14

Corticosteroid-binding globulin aka transcortin

Question 15

Circulating half-life of cortisol?

Answer 15

90 minutes

Question 16

What receptor does CRH work through and review the intracellular pathway?

Answer 16

G-protein coupled receptor-> AC-> cAMP->PKA-> Ca-> ACTH exocytosis

Question 17

What receptor does ACTH bind to in the adrenal cortex?

Answer 17

MC2R (melanocortin-2 receptor)

Question 18

What is the specificity of mineralocorticoids and glucocorticoids to receptors?

Answer 18

Glucocorticoids have a higher affinity than mineralocorticoid receptors and they share receptors (nonspecificity)

Question 19

What prevents the nonspecificity for glucocorticoids to mineralocorticoid receptors and the significance of this?

Answer 19

11-hydroxysteroid dehydrogenase type 2 in mineralocorticoid target cells converts GC to a less active form that allows mineralocorticoids to have higher affinity to the receptors; it allows mineralocorticoids to bind to receptors (if absent then GC would always bind)

Question 20

Aside from 11-hydroxysteroid dehydrogenase type 2, what ensure that MC effects can be mediated in the presence of GC?

Answer 20

Aldosterone (MC) dissociates more slowly from receptors than GC so it is less easily displaced

Question 21

What does 11beta-HSD1 and 11beta-HSD2 do respectively?

Answer 21

HSD1: converts cortisone to cortisol
HSD2: converts cortisol to cortisone

Question 22

How do glucocorticoids ready the innate immune system?

Answer 22

1. ) TLR induction
2. ) NLRP3 inflammasomes and P2Y2R induction
3. ) Increasing IL-6 and IL-8

Question 23

What pro-inflammatory transcription factors do glucocorticoid receptors repress?

Answer 23

AP-1

NF-kappa B

Question 24

Mnemonic to remember cortisol function?

Answer 24

BIG FIB

Question 25

BIG FIB:

Answer 25

Increase: blood pressure, insulin resistance, gluconeogenesis
Decrease: fibroblast activity, inflammatory and immune response, bone formation

Question 26

Summary of action of glucocorticoids?

Answer 26

Hyperglycemia: increase gluconeogenesis and Glycogenolysis
Free FA and AA production
Catecholamine release
Anti-inflammatory/immunosuppressive

Question 27

Mineralocorticoids long-term stress response:

Answer 27

1. ) Retention of Na and water by kidneys

2. ) Increased blood volume -> increased blood pressure

Question 28

Glucocorticoids long-term stress response:

Answer 28

1. ) Proteins and fats broken down and converted to increased blood glucose
2. ) Immune system suppression

Question 29

What is Cushing’s syndrome?

Answer 29

Elevated glucocorticoids long-term (cortisol)

Question 30

What is Addison’s disease?

Answer 30

Insufficient levels of glucocorticoids