The Adrenals and their hormones

Question 1

Where does the left adrenal vein drain into?

Answer 1

Renal vein

Question 2

Where does the right adrenal vein drain into?

Answer 2

Inferior vena cava

Question 3

Blood supply to adrenals

Answer 3

Both have many arteries

Both have only 1 vein

Question 4

What is the structure of the adrenal gland from the outside to the inside?

Answer 4

Zona Glomerulosa (aldosterone)
Zona Fasciculata (cortisol and sex steroids)
Zona Reticularis (cortisol and sex steroids)
Adrenal Medulla (catecholamines)

Question 5

What catecholamines are produced by the adrenal medulla? What are the cells involved called?

Answer 5

Chromaffin cells
Adrenaline (80%)
Noradrenaline (20%)
+ Dopamine

Question 6

What is the adrenal cortex comprised of?

Answer 6

Zona Glomerulosa
Zona Fasciculata
Zona Reticularis

Question 7

What is produced in the adrenal cortex? State the 4 hormones produced.

Answer 7

Corticosteroids:
Mineralocorticoids: aldosterone
Glucocorticoids: cortisol
Sex Steroids: androgens and oestrogens

Question 8

What are steroid hormones synthesised from? What is the consequence of this?

Answer 8

Cholesterol

Lipid soluble, highly influence gene transcription and translation

Question 9

How many carbons in mineralcoricoids, glucocorticoids and androgens?

Answer 9

Mineralocorticoids: C21
Glucocorticoids: C21
Androgens: C19

Question 10

Describe the production of steroid hormones

Answer 10

Lipoproteins deliver cholesterol to cell
Cholesterol stored in cell in fat droplets
Signal causes liberation of cholesterol by Esterase
Cholesterol driven into mitochondria by StAR protein
Cholesterol processed in mitochondria to produce steroid hormone
Different hormones are produced in different areas of the cortex due to presence of different enzymes

Question 11

Whys are only low levels of sex hormones produced in the adrenal cortex?

Answer 11

Low presence of enzymes required to produce them

Question 12

How are corticosteroids transported in the blood?

Answer 12

Bind to plasma proteins.
There is so much albumin that some corticosteroids will non-specifically bind to albumin.
Also more specific plasma proteins: corticosteroid binding globulin (CBG)

Question 13

% of free cortisol and aldosterone in blood?

Answer 13

Cortisol: 10% free
Aldosterone: 40% free

Question 14

What do cortisol and aldosterone bind to?

Answer 14

Cortisol binds to glucocorticoid receptor (GR) and mineralocorticoid receptor (MR)
Aldosterone only binds to mineralocorticoid receptor (MR)

Question 15

What type of hormone can access tissues and bind to relevant receptors?

Answer 15

Free unbound hormone

Question 16

Describe the difference in the blood concentrations of cortisol and aldosterone

Answer 16

Concentration of cortisol is 1000 fold greater than the concentration of aldosterone.

Question 17

How does cortisol concentration vary?

Answer 17

Cortisol concentration changes with the circadian rhythm. Stress hormone, so released more at times of stress.

Question 18

Why do we need aldosterone if cortisol can bind to MR receptors?

Answer 18

Certain tissues (kidney, placenta) have a lot of 11b-hydroxysteroid dehydrogenase 2 enzyme
This breaks down cortisol, so it can't act on that tissue
Necessitates aldosterone

Question 19

Where is renin produced?

Answer 19

Granular cells in kidney

Question 20

What 3 stimuli increase renin production?

Answer 20

Renal Perfusion Pressure (RPP): If BP coming into afferent arteriole drops, sensed by granular cells, causes increased renin production
Renal sympathetic activity: If SNS is activated, renin production increases
Macular densa cells (Na+ sensors) in distal convoluted tubule: low concentration Na+ in filtered fluid, increases renin production

Question 21

What does renin do?

Answer 21

Causes secretion of aldosterone

Increases Na+ reabsorption and water reabsorption Therefore increases BP

Question 22

Mechanism of renin-angiotensin-aldosterone system

Answer 22

Renin acts on Angiotensinogen (from liver)
Produces Angiotensin I
Angiotensin converting enzyme (ACE) (e.g. in lungs) converts AI to AII
AII enters adrenal gland and activates aldosterone producing cells

Question 23

What else can stimulate aldosterone production?

Answer 23

Low blood Na+

High blood K+

Question 24

Describe secretion of cortisol

Answer 24

Corticotrophin releasing hormone (CRH) in hypothalamus is released into bloodstream
CRH delivered to anterior pituitary
Corticotrophs produce adrenocorticotrophic hormone (ACTH)
ACTH passes down to adrenal cortex to stimulate cortisol production
Negative feedback: Cortisol regulates its own production

Question 25

Describe the mechanism of action of aldosterone.

Answer 25

Aldosterone binds to intracellular receptors and translocates to the nucleus and causes changes in transcription Leads to increased number of Na+ channels and Na+/K+ ATPase pumps Upregulates ability to reabsorb Na+ and indirectly increase H2O reabsorption

Question 26

Where does aldosterone effect?

Answer 26

Late distal tubule collecting duct in kidney | Drives Na+ out of the collecting duct and back into blood

Question 27

Cortisol mechanism of action

Answer 27

Cortisol binds to GR receptor in cell Complex translocates to nucleus Change in protein transcription and translation

Question 28

What complexities lie in the mechanism of action of cortisol?

Answer 28

Can bind to 2 receptors (Glucocorticoid and Aldosterone) in most tissues Optimum level of activation = Full MR activation, Partial GR activation

Question 29

Physiological actions of cortisol: Metabolism

Answer 29

Increases hepatic gluconeogenesis Increase glycogenolysis Increases livers capacity to make and store glucose Stops glucose being stored peripherally Reduces blood flow to skeletal muscle and adipose tissue

Question 30

Physiological actions of cortisol: Memory

Answer 30

At physiological levels is pro-memory Stress (and cortisol) wants to imprint memory as a survival technique Cortisol increases capacity of dantate gyrus in hippocampus to respond to serotonin (adds more receptors)

Question 31

Supra-physiological actions of cortisol: | Anti-inflammatory/ Immunosuppressive effects

Answer 31

Cortisol released to control inflammatory response at physiological level As Cortisol levels increase becomes very anti-inflammatory and immunosuppressive (Often become ill when stressed due to high levels of cortisol)

Question 32

Pathological actions of cortisol: memory

Answer 32

Predominantly GR activation long term Chronically high levels of cortisol, negative effect on serotonin (anti-memory effect) Hippocampus gets smaller Cortisol starts destroying hippocampus and impacts ability for long term memory formation

Question 33

Adrenal androgens

Answer 33

Synthesised in zona reticularis | = Dehydroepiandrostenedione (DHEA), DHEAS, androstenedione

Question 34

Dehydroepiandrostenedione biological activity

Answer 34

Weak biological activity | But converted to more active androgens e.g. testosterone by enzymes in peripheral tissues

Question 35

How does DHEA contribute to androgen production in men and women?

Answer 35

Women: substantially contributes to overall androgen production and effects Men: very small contribution to androgen production