HRR: adrenal cortex

Question 1

What are the zones of the adrenal cortex?

Answer 1

Glomerulosa, fasciculata, and reticularis

Question 2

ACTH stimulates which portions of the adrenal cortex?

Answer 2

Zona fasciculata and zona reticularis

Question 3

What is the starting point for steroid synthesis?

Answer 3

C27

Question 4

What is desmolase?

Answer 4

An enzyme that cleaves carbons from cholesterol to help us derive various hormones

Question 5

ACTH stimulates the uptake of…

Answer 5

LDL cholesterol

Question 6

What is STAR?

Answer 6

A protein that transfers cholesterol into the inner mitochondrial membrane

Question 7

Describe cholesterol entering the zona fasciculata.

Answer 7

1. ACTH stimulates uptake of LDL cholesterol
2. Cholesterol is esterified and taken into a vesicle
3. Cholesterol ester hydrolyase forms free cholesterol
4. STAR transfers free cholesterol to the inner mitochondrial membrane

Question 8

What are rate-limiting enzymes of steroid synthesis?

Answer 8

Desmolase and StAR

Question 9

What is formed from cholesterol via initial cleavage by desmolase?

Answer 9

Pregnenolone (C21)

Question 10

What does 17-hydroxylase do?

Answer 10

Adds a hydroxyl group to pregnenolone in the zona fasciculata

Question 11

What does 21-hydroxylase do?

Answer 11

Forms 11-deoxycortisol from 17OH-progesterone

Question 12

What does 11-hydroxylase do?

Answer 12

Forms cortisol from 11-deoxycortisol in the zona fasciculata

Question 13

What does 11B HSD type 2 do?

Answer 13

Breaks cortisol to cortisone, forming an inactive metabolite. This prevents cortisol from setting off too many mineralocorticoid receptors when it shouldn’t

Question 14

Where do we have a lot of 11B HSD type 2?

Answer 14

Kidney and colon (where there’s lots of mineralocorticoid receptors)

Question 15

What does 11B HSD type 1 do?

Answer 15

Forms cortisol from cortisone, the active version. This allows us to utilize cortisol at mineralocorticoid receptors when we want to.

Question 16

What cofactor enhances the 17-hydroxylase complex?

Answer 16

B5

Question 17

What are DHEA, DHEAS, and androstenedione?

Answer 17

Weak androgens that are converted by other tissues to be more potent androgens such as testosterone

Question 18

17OH-pregnenolone can be acted on by 17-hydroxylase to form…

Answer 18

DHEA

Question 19

What does SULT2A1 do?

Answer 19

Form DHEAS from DHEA

Question 20

Where do we make most testosterone?

Answer 20

Most is in the peripheral tissues; some is made in the zona reticularis!

Question 21

DHEA can form…

Answer 21

Androstenedione and testosterone

Question 22

What are binding proteins for cortisol?

Answer 22

CBG and albumin

Question 23

How is bound cortisol used?

Answer 23

It is not! It is still measured in total cortisol

Question 24

What are the functions of binding cortisol?

Answer 24

Stabilizes the hormone, decreases metabolism/extends half-life, creates a reservoir

Question 25

What receptors does cortisol bind?

Answer 25

Intracellular glucocorticoid receptor alpha and mineralocorticoid receptors

Question 26

How does cortisol impact metabolism?

Answer 26

Increases blood glucose and glycogen storage, increases insulin resistance, promotes protein breakdown/decreases synthesis, and increases fat breakdown

Question 27

What are body-habitus effects of cortisol?

Answer 27

“Moon face”, fat deposition in the trunk, and muscle wasting/thin limbs

Question 28

What are cardiovascular effects of cortisol?

Answer 28

Helps maintain BP by acting as a permissive hormone for catecholamines and angiotensin II

Question 29

What is the role of cortisol in inflammation?

Answer 29

It is anti-inflammatory, and acts to depress cytokines, histamines, prostaglandins

Question 30

What is the role of cortisol in terms of the immune response?

Answer 30

It limits circulating lymphocytes and antibody production

Question 31

Describe how cortisol is anti-inflammatory.

Answer 31

When Tissue injury occurs, NFkB translocates to the nucleus and causes genes that encode for pro-inflammatory cytokines, leukotrienes, TNFa, etc to be transcribed. Cortisol binds GR receptors, enters the nucleus, and the complex lands on the genes NFkB targets, blocks its effects. Cortisol thereby decreases release of pro-inflammatory chemical mediators

Question 32

What is Addison’s disease?

Answer 32

Adrenal gland loss associated with bronzing of the skin/hyperpigmentation, general fatigue, and heart symptoms from increased ACTH

Question 33

What is Cushing’s disease?

Answer 33

Overproduction of ACTH and cortisol leading to loss of musculature and muscle weakness, truncal obesity, hyperglycemia, and hypertension