Adrenal Physiology

Question 1

Review: 3 layers of the cortex from the outside in? What does each do?

Answer 1

GFR–> Medulla
Glomerulosa - Salt (Aldosterone)
Fasciculata - Sugar (Glucocorticoids)
Reticularis - Sex (Androgens)

Medulla- STRESS ( Epinephrine, Norepinephrine)

Question 2

What class of molecule are the hormones made in the adrenal cortex? What are they all derived from?

Answer 2

Steroid class

- All derived from cholesterol

Question 3

Do steroids only bind to nuclear receptors?

Answer 3

No, they can also modify enzyme activity by binding surface receptors.

Question 4

What is the rate limiting step of all steroidogenesis?

Answer 4

Cleavage of cholesterol to pregnenolone by CYP11A1 in the mitochondria.

Question 5

What steroid hormone synthesis enzyme is located only in the zona glomerulosa?

Answer 5

Aldosterone Synthase (makes aldosterone from corticosterone)

Question 6

What are 3 things that drive aldosterone release?

Answer 6

1) Increased angiotensin II.
2) Increased serum K+.
3) Increased ACTH. (Lesser stimulus)

Question 7

2 things that drive cortisol release?

Answer 7

1) ACTH

2) Arginine vasopressin (Lesser stimulus)

Question 8

What drives androgen release from the adrenal cortex?

Answer 8

ACTH.

Question 9

Upon what hormone from the adrenal cortex is catecholamine synthesis dependent?

Answer 9

Cortisol

Question 10

Where are the juxtoglomerular cells? What do they do? (What do they make?)

Answer 10

They surround the afferent arterioles to glomeruli and near the distal tubules in the kidney.

• Can sense changes in blood volume
• Sense perfusion pressure
• Sense [Na+] in distal tubule

They make renin.

Question 11

2 ways to stimulate renin production?

Answer 11

1) Low volume in the afferent arterioles.

2) Decreased Na+ concentration in the distal tubule.

Question 12

2 ways to decrease renin?

Answer 12

1) Increased afferent arteriole volume.

2) Increased Na+ concentration in the distal tubule.

Question 13

What does renin do? What are the downstream effects of this?

Answer 13

Renin converts Angiotensinogen to Angiotensin I.
Angiotensin I is converted to Angiotensin II by ACE.
Angiotensin II stimulates aldosterone release.
Aldosterone increases water and Na+ resorption (and increases K+ secretion).

Question 14

2 Main effects of aldosterone? How does it do that?

Answer 14

1) Increases blood volume
2) Regulate salt/water homeostasis
- Increases Na+ absorption and K+/H+ excretion.
- It does this by up regulating Na+/K+ channels in the distal cortical collecting duct. (more on this in renal)

Question 15

3 ways to increase ACTH release?

Answer 15

1) CRH.
2) Arginine vasopressin.
3) Inflammatory cytokines.

Question 16

What is the receptor for ACTH?

Answer 16

Melanocortin 2 receptor.

Question 17

What does ACTH binding to its receptor do? (2 things)

Answer 17

1) Increases LDL receptors -> more cholesterol brought into cell.
2) Increases CPY11A1 expression for steroid synthesis.

Question 18

Review: How is ACTH synthesized, and what else is made with it?

Answer 18

As a long molecule called POMC. Melanocyte stimulating hormones are part of POMC, and released simultaneously with ACTH.

• ACTH has weak affinity for Melanocortin Receptor 1
• When there is huge amount of ACTH–> it can bind to MR1 and result in hyper pigmentation

Question 19

Cortisol has a lot of effects. What effects does it have on bone and skeletal muscle?

Answer 19

Bone: increases osteoclast activity -> osteoporosis.

Skeletal muscle: Amino acid release, insulin resistance.

Question 20

Review: To what hormone does the mineralcorticoid receptor have the highest affinity? How does the body accomodate? (Explain the cortisol shunt)

Answer 20

Mineralcorticoid receptor actually has higher affinity for cortisol than it does for aldosterone
(Our body has way more cortisol than aldosterone)
In aldosterone-sensitive tissues, such as the kidney, cortisol is converted to cortisone ( Which is inactive–> lets aldosterone bind)

Question 21

What enzyme converts cortisol to cortisone?

Answer 21

11-beta HSD2. (hydroxysteroid dehydrogenase)

…it’s been mentioned a few times.

Question 22

What pharmacological activity does licorice have? What does an overdose cause?

Answer 22

It inhibits 11-beta HSD2 (Inactivates Cortisol Shunt–> thus more cortisol, less cortisone)
Overdose mimics hyperaldosteronism -> HYPERtension and HYPOkalemia.

Question 23

What happens to androstenedione in peripheral tissues?

Answer 23

It gets converted to testosterone and estrone.

Question 24

Review: What tells the adrenal medulla to release catecholamines?

Answer 24

Sympathetic nervous system activation

Question 25

B&B Review: What starting product are catecholamines made from? What is the rate limiting step and what enzyme does it? What enzyme converts NE to Epi?

Answer 25

NE and Epi (and dopamine) are made from tyrosine.
RLS: Tyrosine –> Dopa by Tyrosine Hydroxylase.
NE–> Epinephrine by PNMT

Question 26

What specific effects does cortisol have on chromaffin cells?

Answer 26

Cortisol causes upregulation of PNMT, such that the adrenal medulla secretes more Epi (80%) than NE.

Question 27

What are catecholamines converted to in the blood?

Answer 27

Metanephrines… which have also have a short half life. These are all then converted to VMA.
(this is probs pretty low yield)

Question 28

What’s the main point about the different adrenergic receptors, for this lecture?
What do alpha1 and beta2 receptors do?

Answer 28

They’re in different places, and have different activities.
Alpha1 causes peripheral vasoconstriction -> increased BP.
Beta2 causes vasodilation in vessels supplying heart and skeletal muscle, and bronchodilation.

ALL act on the different elements of the Fight or Flight Response

Question 29

What is the main site of androgen production in women? What is it in men?

Answer 29

In women: adrenal glands (ovaries make minor component)

In men: testes (adrenal glands minor component)