Adrenal Cortex

Question 1

List the three layers of the cortex of the adrenal gland and what they produce in response to

Answer 1

GFR

• glomerulosa: mineralcorticoid–> aldosterone (in response to Ang II
• fasciculata: glucocorticoid –> cortisol (in response to ACTH)
• reticularis: DHEA and DHEAS in response to ACTH

DHEA=dehydroepiandrosterone
S=sulfate

Question 2

Describe innervation and type of innervation contained in inner medulla

Answer 2

-contains post-ganglionic sympathetic “nerves” called Chromaffin cells that produce Epi and NE in response to pre-ganglionic sympathetic (cholinergic/nictonic) stimulation

Question 3

Receptor for cortisol

Answer 3

binds to glucocorticoid receptor

-also can bind to mineralcorticoid receptor which is normally bound by Aldo

Question 4

Review how cholesterol obtained, stored, mobilized, and transferred into the inner mitochondrial matrix of the Zone Fasciculata

Answer 4

1) LDL and HDL bind to receptors on cell membrane (LDL-R and SRB1 respectively)
2) get taken up into lysosome with aid of Neimann Pick C transporters
3) get converted to FC
4) FC can then turn into CE (HSL) and get stored as a fat droplet of cholesterol esters
5) can get converted back via ACAT
6) free cholesterol released from lysosome will get transferred to inner mitochondrial membrane via StAR protein where it will it will undergo subsequent reactions to make steroids.

Question 5

Cyp11A1

Answer 5

Converts free cholesterol to P5 (pregnenolone)

-generates a 21 carbon steroid precursor by removing a side chain

Question 6

3βHSD (3β Hydroxysteroid Dehydrogenase)

Answer 6

converts P5 to P4 (pregnenalone –> progesterone)

• can also produce 17-hydroxyprogesterone
• changes the 5-6 double bond to 4-5 double bond and converts the ketone at position 3 to a hydroxyl
• ALL ACTIVE STEROIDS HAVE TO UNDERGO THIS RXN

Question 7

CYP17 (17 hydroxylase function)

Answer 7

• 17 hydroxylase function in fasciculata AND reticularis
• 17/20 lyase in reticularis at adrenarche
• produces either 17-hydroxy-P4 or 17-hydroxy-P5

Question 8

CYP21

Answer 8

main pathway: converts 17-hydroxy-P4 to deoxycortisol (which then gets converted to cortisol)
side pathway: converts P4 to DOC (deoxycortisone) (which then gets converted to corticosterone)
via 21 hydroxylation

Question 9

What does DOC act as? (deoxycorticosterone)

Answer 9

as a mineralcorticoid (like aldo)

Question 10

What enzyme deactivates cortisol to cortisone in the distal nephron so that it does not act on the mineralcorticoid receptor?

Answer 10

11βHSD2

this is important because cortisol is NOT regulated by AngII–it is regulated by stress pathway. You don’t want cortisol binding to MR and activating aldo type actions every time you’re stressed.

Question 11

CYP11B1

absolutely specific to what region

Answer 11

main pathway: deoxycortisol –> cortisol
side pathway: DOC–>corticosterone

zone fasciulata

Question 12

If CYP11B1 activity is deficient, then very high levels of ____ will be made

Answer 12

DOC (which acts like Aldo)

Question 13

Actions of cortisol-fasting state on liver:

Answer 13

liver

• directly increases GNG
• increases adrenergic receptors for actions of catecholamines on glycogenolysis, GNG, and ketogenesis

Question 14

Actions of cortisol-fasting state on skeletal muscle:

Answer 14

• increase adrenergic receptors to increase proteolysis (substrate for GNG)
• decrease GLUT4 in cell membrane

Question 15

Actions of cortisol–fasting state on adipose tissue:

Answer 15

• increase lipolysis

- decrease GLUT4 in cell membrane

Question 16

Actions of cortisol–fed state on liber

Answer 16

-synergizes with insulin to promote glycogen synthesis

helps keep liver well-stocked

Question 17

Actions of cortisol–fed state on adipose tissue

Answer 17

-synergizes with insulin to promote differentiation of pre-adipocytes to adipocytes

(so can store fat)

Question 18

3 main effects of hypercortisolism

Answer 18

1. hyperglycemia (with poor delivery to some tissues)
2. high circulating free fatty acids, but also deposits of adipose tissue at specific sites (face, abdomen, intrascapular)
3. muscle wasting of limbs and weakness