Endo 7 - the adrenals and their hormones

Question 1

What is particular about the venous drainage of the adrenals?

Answer 1

Left adrenal vein drains into the IVC
Right adrenal vein drains into right renal vein

(Both adrenals have many arteries but one vein)
The fact that it has one vein means blood comes from the outside to the medulla where there is the central vein so corticosteroids produced by cortex will pass through medulla and have an effect on cathecolamines

Question 2

List the zones of the adrenals from outside to inside

Answer 2

Zona glomerulosa
Zona fasciculata 
Zona reticularis
--> these form the adrenal cortex
Adrenal medulla (chromaffin cells)

Question 3

What type of hormone is secreted by the adrenal cortex?

Answer 3

Corticosteroids

Question 4

What type of hormone is secreted by the adrenal medulla?

Answer 4

Cathecolamines:
- Adrenaline (=epinephrine) 80%
- Norarenaline (=norepinephrine) 20%
(Dopamine)

Question 5

What hormone does zona glomerulosa produce?

Answer 5

Aldosterone (=mineralcorticoid)

Question 6

What hormone does zona fasciculata produce?

Answer 6

Cortisol (=glucocorticoid) and sex steroids

Question 7

What hormones does zona reticularis produce?

Answer 7

Cortisol and sex steroids

Question 8

What is the common step between cortisol, aldosterone and sex steroids production?
What next step is common to which two of these but not the third?

Answer 8

First step is common to all 3 is the conversion of cholesterol to pregnenolone by P450scc.
Then aldosterone has a different next step but cortisol and sex steroids have the same: conversion of pregnenolone to 17alpha-pregnenolone by P450c17.
For aldosterone, pregnenolone is converted to progesterone.

Question 9

What is androstenedione?

Answer 9

It is a weak androgen that can be converted to testosterone and dihydrotestosterone

Question 10

How many carbons in mineralcorticoids, glucocorticoids, progestogens, androgens, oestrogens?

Answer 10

mineralcorticoids C21
glucocorticoids C21
progestogens C21
androgens C19
oestrogens C18

Question 11

How are corticosteroids transported in the blood?

Answer 11

They bind to plasma proteins.
There is so much albumin that some corticosteroids will non-specifically bind to albumin.
There are more specific plasma proteins - corticosteroid binding globulin
Aldosterone is quite a free hormone - 40% unbound compared to cortisol 10%

Question 12

Describe the difference in the blood concentrations of cortisol and aldosterone.

Answer 12

The concentration of cortisol is 1000 times greater than the concentration of aldosterone.

Question 13

How does cortisol concentration vary?

Answer 13

Cortisol concentration changes with the circadian rhythm. It is a stress hormone so is released more at times of stress.
Released in a pulsatile fashion as it follows the hypothalamus

Question 14

On which receptors can cortisol act? Aldosterone? (corticosteroids)

Answer 14

Cortisol can bind to both the Glucocorticoid Receptor (GR) and the Aldosterone receptor (MR)
Aldosterone can bind to MR only

NOTE
To prevent Cortisol from over-activating the MR receptors in the body, there is a specific enzyme in the kidney called 11β-Hydroxysteroid Dehydrogenase 2. This converts Cortisol into the inacyive form Cortisone.

Question 15

Which steps in the synthesis of aldosterone are important in terms of diseases?

Answer 15

progesterone —> deoxycorticosterone —> corticosterone (—> aldosterone)
by enzymes 21 hydroxylase and 11b-hydroxylase. Defienciency of these enzymes are common.
Deoxycorticosterone and corticosterone still have some mineralcoticoid activity so deficiency can be balanced although aldosterone synthesis is very important as it is the most potent.
These enzymes are also used in the synthesis of cortisol:
17a-hydroxyprogesterone —> 11b-deoxycortisol —> cortisol

Question 16

Why do you need aldosterone if cortisol can bind to the MR receptor?

Answer 16

Because some tissue will exclude cortisol like the kidneys so only aldosterone can access them.
Does this by inactivating cortisol with enzyme 11b-hydroxysteroid dehydrogenase 2

Question 17

What 3 stimuli induce Renin secretion by the kidneys?

Answer 17

1. Decreased RPP
2. Increased renal Sympathetic activity (on beta1 adrenergic receptors) as a result of trying to increase BP. Effect on GRANULAR CELLS (endothelium)
3. Decreased Na+ Load in distal tubule - change detected by MACULAR DENSA CELLS
   Because low Na load–> Na gets out of cells –> cells shrink –> signal that you need to keep Na so –> renin

Question 18

Describe the RAAS system after Renin secretion from the kidneys has been induced by the 3 different stimuli?

Answer 18

Liver is the source of another plasma protein – ANGIOTENSINOGEN
When the juxtaglomerular cells of the renal afferent arteriole secrete RENIN, this breaks off a peptide from angiotensinogen to form ANGIOTENSIN I
Angiotensin I is then converted by ACE (Angiotensin Converting Enzyme, found in the epithelia of the lungs and kidneys) to form ANGIOTENSIN II

Effects of angiotensin II:
Vasoconstriction
Stimulates the ZONA GLOMERULUS of the adrenal cortex to synthesise and release ALDOSTERONE.
This leads to increased Na+ reabsorption in the distal convoluted tubule, therefore increasing water reabsorption which in turn increases the volume of the ECF (blood) – increasing BP

NOTE
Chronic fluid retentionincrease can lead to high blood pressure (hypertension). Therefore ACE inhibitors are main antihypertensives used.

Corticotrophin (released from the anterior pituitary gland) also stimulates aldosterone release. However, the effect of ACTH is very minor, and not really significant.
Increased K+ and decreased Na+ also stimulates aldosterone release. This occurs at the level of the adrenals.

Question 19

What are the effects of aldosterone?

Answer 19

Increased potassium and H+ secretion

Increase sodium reabsorption

Question 20

Describe the hypothalamo-pituitary-adrenal axis for cortisol release

Answer 20

CRH by hypothalamus –> corticotrophs on pituitary –> ACTH –> adrenals –> cortisol production
Cortisol exerts negative feedback on pituitary and hypothalamus

Question 21

Describe the mechanism of action of aldosterone.

Answer 21

Aldosterone binds to intracellular receptor MR and translocates to the nucleus and causes changes in transcription leading to the synthesis of sodium ion channels (lumen membrane of distal tubule cell) and sodium ATPase.
This means sodium can diffuse into cell (channels) and also increases cell capacity to export Na into the blood (pumps)
No direct effect on water but as it drags sodium, water comes with

Question 22

What are the effects of cortisol?

Answer 22

Physiological effects
Metabolic Effects 
Peripheral protein catabolism 
Hepatic gluconeogenisis 
Increased blood glucose concentration 
Lypolysis in adipose tissue 
Enhanced effects of glucagon and catecholamines 

Mineralocorticoid effects (like aldosterone)

Renal and Cardiovascular Effects
Excretion of water load
Increased vascular permeability

Other effects
Bone growth
CNS effects

Question 23

What is the precursor of ACTH?

Answer 23

POMC

Question 24

What are the three effects of large amounts of cortisol?

Answer 24

Supra-physiological - pharmacological

1. Anti-inflammatory action
2. Immunosuppressive action
3. Anti-allergic action

Question 25

What is the precursor of ACTH?

Answer 25

POMC

Question 26

What makes long term cortisol bad?

Answer 26

Normal physiological cortisol –> maximum MR and low GR activation
However long term stress –> maximum MR and GR activation

Question 27

What is dehydroepiandrostenedione (DHEA)?

Answer 27

Androgen produced by the adrenal, synthesised in zona reticularis.
Weak biological activity - but converted to more potent androgens