Adrenal physiology

Question 1

1. Identify the key steps in steroid hormone biosynthesis.

Answer 1

Cholesterol goes to pregnenalone

pregnenalone can be made into mineralocorticoids

pregnenalone can also hydroxylated into 17-OH=pregnanlone which can turn into glucocorticoids or it can be tuened into DHE and then sex steroids

Question 2

2. Describe the transport of glucocorticoids in the plasma.

Answer 2

> 90% carried by carrier proteins (cortisol-binding-proteins)

-hard to estimate free concentration, eventhough this portion is important and regulated

Question 3

3. Categorize the actions of cortisol on various systems.

metabolic
CV
Fibroblasts
Vit D
inflammatory
immune

Answer 3

metabolic

• glucose up, gluconeogenesis up, insulin down
• proteins freed from muscle
• FFA freed, in excess deposited centripedally (moon facies, Buffalo hump)

CV (permissive effects)

• increase HR, Increase contractiloty by uprgeulated Beta adrenergic receptors
• increase RBC’s (polycythemia)

Fibroblasts

• decreases their production
• decrease fibroblast #
• decrease collagen synthesis (thinning of the skin)

Vit D- antagonizes vit D

• osteoporosis
• Ca2+ deficiency

Antiinflammatory

• inhibits Phospholipase A2
• less arachodonic acid-> less PGs, LKT’s, TXA’s
• inhibits vascular permeability changes

Immunosupression

• inhibits T cell Proliferation
• inhibits T cell Activation

Question 4

4. Diagram the regulation of ACTH production and release.

Answer 4

Cortisol neg feedback on Hypothalamus production of CRH

cortisol neg feedback on ant. pituitary on ACTH

Question 5

5. Define the actions of ACTH.

Answer 5

acts on Adrenal cortex

• increases cell #
• increases enzyme #

Question 6

6. Define mechanisms of epinephrine release from medullary chromaffin cells.

Answer 6

Tyrosine is converted to L dopa by TYR-hydroxylase

L-dopa is converted to dopamine by Dopa decarboxylase

Dopamine goes into dense core vesicles (chromogranins) where its converted to NE by Dopa Beta Hydroxylase,

NE exits vesicle through H+/NE cotransporter where is is converted to EPI and shuttled back in through same mechanism

Splanchnic nerve through nicotinic neuronal receptors relases Ach causing Na+ influx depolarizing the cell, causing Ca2+ influx causing vesicle relases from chromaffin cells

There is also a slow mechansim through muscurinic receptors

Question 7

7. Describe the body’s integrated response to stress.

Answer 7

glucose goes up (glycogenolysis)

free fatty acids go up (stimulated HSL)

Insulin release drops (protect from HYpoglycemia (alpha/beta high)
-alpha decreases cAMP, Beta increases cAMP

Question 8

8. Describe actions of epinephrine and mechanisms of adrenergic receptor action.

Answer 8

Beta- Gs->AC->increase cAMP
Alpha 2- Gi/o-> decreases cAMP
Alpha 1- Gq-> IP3, DAG-> increase Ca2+ and PKC

Question 9

Adrenal insufficency

Answer 9

addisons disease

• Cortisol down
• ACTH up
• Aldosterone down

Question 10

Pituitary insufficiency

Answer 10

ACTH down, cortisol down, normal aldosterone due to renin aldosterone angiotensin system

Question 11

Cushings syndrome

Answer 11

pituitary- (cushings disease) 
-increased ACTH, increased cortisol
Adrenal
-increased cortisol, decreased ACTH, -increased aldosterone
exogenous cushings
-too many steroids

Question 12

Pheochromocytoma

Answer 12

Pathological increase in Catecholamines

Question 13

Regulation of MEdulla

Answer 13

Spinal cord- aplanchnic nerve, short burst no need for feedback

Cortisol-> acts on medulla increases NE, E release
-> increases B adrenergic activity by increasing Bets receptors

Brain (hypothalamus)

• CRH and NE can excite each other
• arousal and agression