Adrenal Glands

Question 1

List the layers of the adrenal gland in order (out-to-in) and what each produces.

Answer 1

1. Zona glomerulosa (mineralocorticoids)
2. Zona fasciculata (glucocorticoids)
3. Zona reticularis (androgens)
4. Adrenal medulla (catecholamines)

Question 2

Which two factors stimulate aldosterone release from the zone glomerulosa?

Answer 2

1. Hyperkalemia

2. Angiotensin 2

Question 3

Steps in cortisol synthesis

Answer 3

1. ACTH activates adenyl cyclase, which converts ATP (from glycolysis) to cAMP
2. cAMP activates Protein Kinase A
3. Protein Kinase A promotes cholesterol ester -> cholesterol
4. Desmolase converts cholesterol to pregnenolone

Question 4

What is the rate-limiting step in adrenal steroid biosynthesis?

Answer 4

Cholesterol -> pregnenolone (side chain cleavage, mediated by desmolase)

Question 5

Describe species differences in cortisol v corticosterone

Answer 5

Cats, sheep, and primates = Cortisol > Corticostreone

Dogs = equal amounts of each

Birds, reptiles, amphibians, mice, and rats = Corticosterone > cortisol

Question 6

Which organs convert cortisol to cortisone and which enzyme catalyzes this conversion?

Answer 6

Kidney and liver
HSD-2

HSD-1 can restore cortisone to the more potent cortisol

Question 7

Compare and contrast cortisone and corticosterone

Answer 7

Cortisone has weaker glucocorticoid activity than cortisol

Corticosterone has even weaker glucocorticoid activity but has strong mineralocorticoid activity

Question 8

What transports most of the cortisol in plasma?

Answer 8

Transcortin (note that cortisol is inactive when bound; more bound than free in plasma)

Question 9

Cushing’s vs Addison’s

Answer 9

Cushing's = hi cortisol
Addison's = lo cortisol

Question 10

Effects of glucocorticoids on liver

Answer 10

1. Stimulates gluconeogenesis
2. Stimulates hepatic glycogenesis
3. Increases blood glucose
4. Increases angiotensinogen, leading to hypertension

Question 11

Effect of glucocorticoid on adipose

Answer 11

1. Lipolysis (liver then uses FFAs for TG and ketone body synthesis)
2. Increase hormone-sensitive lipase
3. Decrease glucose uptake

Question 12

Effect of glucocorticoid on muscle/bone

Answer 12

Catabolic (negative nitrogen balance)

i.e. degrades proteins and inhibits protein synthesis

Question 13

Glucocortidoids have _____ effects on the liver and _____ effects on muscle, fat, connective tissue, and lymphoid tissue.

Answer 13

Anabolic

Catabolic

Question 14

Effect of glucocorticoid on pituitary

Answer 14

1. Downregulates all 6 products of anterior pituitary and ADH from neurohypophysis
2. Consequence of decreased TSH is decreased LDL receptors -> increased plasma cholesterol

Question 15

Synergistic effects of amines (thyroid hormones and catecholamines) and cortisol

Answer 15

1. Thyroxine alone has no effect on adipoctye
2. Epinephrine alone causes small amount of FFA release
3. Cortisol + thyroxine + epinephrine = large FFA release

Question 16

Regulation of lipolysis

Answer 16

1. Catecholamines bind B1-receptor
   a. T4, T3 increase B1- receptor
2. Binding activates adenyl cyclase
3. cAMP activates protein kinase
4. Protein kinase phosphorylates/activates HSL
   a. Glucocorticoids promote HSL synthesis

Question 17

Effect of glucocorticoid on Bone and CT

Answer 17

1. Hypocalcemia
   a. Increased PTH
   b. Decreased osteoblast protein synthesis
   c. Decreased bone mass
2. Decreased fibroblast activity
   a. Decreased muscle and thin skin
3. Decrease in Type 1 collagen synthesis contributes to both the decreased bone mass and decreased skin thickness

Question 18

Steps in Prostaglandin and thromboxane synthesis (how glucocorticoids suppress inflammatory response)

Answer 18

1. Phospholipase A2 converts membrane phospholipid to arachidonic acid
   a. Glucocorticoids suppress PLA2
   b. Angiotensin 2 promotes PLA2
2. COX 1 and 2 convert arachidonate to prostaglandins and thromboxanes
   a. Glucocorticoids inhibit COX-2
   b. NSAIDs inhibit both COXes

Question 19

How do glucocorticoids contribute to ulcers?

Answer 19

1. Decrease prostaglandin production (via PLA2 and COX2 inhibition)
   a. Increase Hcl
   b. Decreases
   HCO3/mucus
2. Decreased COX2 inhibits repair

Question 20

Effect of glucocorticoid on duodenum

Answer 20

Decreased Ca absorption due to blunted Vitamin D

Question 21

How do glucocorticoids contribute to hypertension?

Answer 21

1. Increase Cardiac Output
2. Decrease endothelium permeability
3. Increases responsiveness to constrictors (NE and angiotensin 2)
4. Decreases responsiveness to dilators (prostaglandins and NO)

Question 22

Causes of glucocorticoid excess

Answer 22

1. Pituitary tumor: ACTH -> cortisol [Cushing’s DISEASE]
2. Adrenocortical tumor: increased cortisol and decrease ACTH [Cushing’s syndrome]
3. XS glucocorticoid therapy (same as C syndrome)

Question 23

Causes of glucocorticoid deficiency

Answer 23

1. Autoimmune destruction of adrenal cortex/pituitary

2. Treatment w/ adrenal suppressors OR body’s reaction after prolonged glucocorticoid therapy

Question 24

Cushing’s Disease

Answer 24

Cortisol: hi
ACTH: hi

Question 25

Cushing's syndrome

Answer 25

Cortisol: hi ACTH: lo

Question 26

Addison's disease

Answer 26

Cortisol: lo ACTH: hi

Question 27

Pituitary insufficiency

Answer 27

Both ACTH and Cortisol are lo

Question 28

Aldosterone actions

Answer 28

Increases blood pressure: a. Increases salt/water absorption (at expense of potassium) Angiotensin 2 (stimulates aldosterone release) is a vasoconstrictor

Question 29

Name the four sites of aldosterone action

Answer 29

1. Principal cells of distal tubules (inserts Na/K pump and Na channels) 2. Salivary and sweat glands 3. Skeletal muscle 4. Large intestine

Question 30

Where does conversion of androgen to estrogen take place, and which enzyme catalyzes this conversion?

Answer 30

Adipose | Aromatase

Question 31

Steroid fates

Answer 31

1. Androgens -> keto steroids -> sulfates -> urine/bile 2. Aldosterone and corticosterone -> tetrahydro-derivatives -> glucouronides -> urine/bile a. Remember b/c aldosterone and corticosterone both have mineralocorticoid activity 3. Cortisol/cortisone can go through the keto steroid route, the tetrahedron-derivate route, or directly to sulfates

Question 32

How does aldosterone contribute to ascites?

Answer 32

When liver is damaged, albumin production and therefore plasma oncotic pressure decreases leakage of fluid out of blood vessels triggers RAAS system, which promotes water retention via aldosterone (but this water does not stay in blood vessels and contributes to swelling)

Question 33

Loss of the adrenal cortex is fatal due to the loss of which steroids?

Answer 33

1. Glucocorticoids | 2. Mineralcorticoids