The adrenals and their hormones Flashcards
Location and anatomy of the adrenal gland
It is embedded on the superior poles of the 2 kidneys- they have their own capsules.
Left adrenal vein drains into renal vein before reaching the vena cava
Right adrenal vein drains into IVC (inferior vena cava)
Both adrenals have MANY arteries but just one vein. You want lots of blood delivering the substrate to gland. Collects in the middle and diffuses out. Vein is central- in the middle of the medulla
Histology of the adrenal glands- what are the different areas?
Adrenal medulla- in the centre of the gland
Then in order from inside to outside:
Zona Reticularis
Zona Fasciculata
Zona Glomerulosa
The three outer layers that surround the medulla are collectively known as the adrenal cortex
What are the main products from the medulla and the cortex?
Medulla- catecholamines (adrenaline (80%) and noradrenaline (20%) and some dopamine)
Cortex- corticosteroids
Different zones produce different corticosteroids
Mineralcorticoids- aldosterone
Glucocorticoid- cortisol
Sex steroids- androgems and oestrogens
What surrounds the adrenal gland?
A tough fibrous capsule
What parts of the cortex produce what?
Zona glomerulosa- aldosterone (mineralcorticoids)
Zona fasciculata and reticularis- cortisol and sex steroids
Synthesis of adrenal gland hormones
They are all steroid hormones so are produced from cholesterol.
Gonadal steroids are slightly different- they are cleaved
Steroid hormone synthesis
Lipoproteins deliver cholesterol to the cell. The cholesterol is stored as fat droplets inside the cell.
When the right signal comes along, the cholesterol is liberated by esterase and cholesterol is driven into the mitochondria by StAR proteins. Here it used to produce the steroid hormone.
Importance of the types of enzymes in cortex
Cholesterol can undergo many different modifications by different enzymes. Therefore, the hormone that is produced by a certain zone of the cortex depends on the enzyme that is present there.
C17 enzyme in cortisol
Aldosterone synthase present in the zona glomerulosa- diversion you don’t get cortisol, you get corticosterone.
Why do you get a small number of sex steroids
They need extra enzymes to make these (blue ones)
Theres only a few number of these enzymes present so there aren’t vast amounts produced.
How are steroid hormones transported in the blood?
Diffuse very quickly out of the cells that produce them
Housekeeping protien- loose binding (albumin)
Or specific binding globulins: CBG- corticosteroid binding globulin- bind to cortisol and aldosterone
Therefore you have a circulating store of the steroid hormone- they just have to be released.
Cortisol is massively plasma protein bound- small free pool.
Aldosterone- most is bound to proteins but fair amount is in free pool
Why is it important that there are free unbound hormone?
Only free unbound hormone can access tissues and bind to relevant receptors.
Cortisol binds to glucocorticoid receptor (GR)
Aldosterone binds to mineralcorticoid receptor (MR)
If there is something that is heavily protein bound, small changes in the free pool has A HUGE change- if 5% of cortisol is displaced from CBG, there is a 50% increase in the free pool (10%-15%)
Cortisol and aldosterone release throughout the day
cortisol: Diurnal rhythm (changes)
Highest when you wake up and lowest when you go to sleep.
Aldosterone: 1000-fold difference in concentration- much less than cortisol
Remains the same all day
Hormones relationship with receptors
Cortisols bind to Glucocorticoid receptors (GR)
Aldosterones bind to Mineralcorticoids receptors (MR)
Cortisol is NOT selective, it can also bind to MR
So cortisol= MR and GR
Aldosterone= MR
If cortisol can bind to both MR and GR, what is the point of aldosterone?
Enzyme 11 beta HSD 2 (11beta-hydroxysteroid dehydrogenase type 2)
is a cortisol metabolising enzyme- breaks down cortisol.
As a result, certain tissues have a lot of this enzyme, if so, then cortisol cannot get in that tissue. Certain tissues are protected from cortisol because if they enter, it wil be broken down. Therefore aldosterone is relevant and can have its effect and bind to MR (i.e in the kidney)
Enzyme is also in the placenta preventing maternal cortisol getting to the foetus. Cortisol can have negative effects on foetus- makes the baby small.
Renin-angiotensin-aldosterone system
System to release renin and maintian bp
It is linked to aldosterone production.
Renin production- comes from granular cells in the kidney.
Various stimuli can increase renin production
What causes increase in renin production?
Renal profusion pressure (RPP)- if bp in afferent arteriole drops, the change is sensed by the granular cells and they churn out lots of renin
Renal Sympathetic nerves- sympathetic nervous activity activated and increase in renin production.
Macula densa cells- within the distal convoluted tubule (which is near the afferent arteriole). There are sodium sensors inside the cell. If the sodium concentration within the lumen of the dct goes down, this stimulates renin production.
What does renin do?
Renin= increase sodium reabsorption, water is reabsorbed and bp is maintained.
What happens after renin is released?
Leads to aldosterone production
Renin is an enzyme acts on protein that comes from the liver- angiotensinogen. Renin activates it producing angiotensin 1.
Certain tissues (like lungs) have angiotensin converting enzyme, it converts angiotensin 1 to angiotensin 2. Angiotensin 2 comes into adrenal glands, enters zona glomerulosa and stimulates aldosterone production.
How is cortisol produced?
Hypothalamo-pituitary-adrenocortical axis
Hypothalamic factors act on anterior pituitary. Hypothalamus releases CRH to anterior pituitary. CRH acts on corticotrophs in the pituitary to stimulate release of ACTH. ACTH goes to adrenal cortex to stimulate cortisol production.
Anterior pituitary and hypothalamus experience negative feedback by the cortisol produced to stop production.
Where does aldosterone act?
Aldosterone has effect on kidney. as fluid passes through kidney to urine, things are reabsorbed. Aldosterone acts in the late distal tubule/ collecting duct.
What does aldosterone do in the kidney?
Aldosterone deals with sodium. Drives it out of the collecting duct back to blood.
Sodium channel (tubule lumen) and sodium/potassium ATP pump (on interstitium side)
Na will diffuse through channel due to conc gradient. ATPase will pick the sodium up and dump it in the blood on the interstitium side. There will be a certain amount of potassium loss.
Aldosterone is a steroid hormone (slow acting becuase it changes transcription)- increases number of sodium channels and sodium/potassium ATP channels. Basically upregulates distal tubule cell’s ability to take in sodium. Vasopresin system is largely linked as water follows.
There are optimal levels for cortisol function- what are the combination of receptors it should bind to?
Bind strongly to MR and bind partially to GR for optimal activity.
in times of stress, you go to maximal GR and return back as quickly as possible.
Role of cortisol
Cortisol has profound effect on glucose. Makes sure that glucose stores are well filled and available.
It is a stress hormone- need glucose to cope. Cortisol makes sure its there for you.
Cortisol increases gluconeogenesis and glycogenolysis by increasing production of certain enzymes in the liver (in particular PepCK which is rate limiting). Cortisol allows the liver to utilise amino acids and anything else to increase the HGO.
It also increase some of the enzymes to allow the glucose to be stored as glycogen.
It stops glucose being stored peripherally as its not accessible. It decreases blood flow to peripheral energy sources.
Prevents glucose from entering cells, decrease in GLUT 4, preventing it being storedin skeletal muscle.
Role of cortisol on memory
Pro-memory
Stress and therefore cortisol imprint memory.
Hippocampus dentate gyrus where new memories are produced. Serotonin is needed to promote memory formation. Cortisol increases the capacity to respond to serotonin (put more receptors in place in this region).
Anti-inflammatory/ immunosuppressant effects and steroids
Cortisol is anti-inflammatory.
Homeostatic response- any inflammatory reaction needs to be switched off. As cortisol increases, it will be irrespective of what is going on in the body. This is why you get ill when you get stressed- more susceptible to disease.
What other factors are associated with high levels of alcohol?
Caffeine and alcohol.
Cortisol levels are higher for both these groups.
Cortisol memory effect
If you have high levels of cortisol, then you are at the tail ends of the u shaped graph. Excessive GR activation, will have negative effects on serotonin. Less memory. Hippocampus will shrink if stressed. Cortisol will destroy this area and long term memory won’t really be a thing anymore.
Adrenal androgens
weak biological activity. If adrenal cortex is overactive then there is a lot of sex steroids.
Remember that they are synthesised in the zona reticularis
Women- adrenal production of DHEA and DHEA-S contributes substantially to overall androgen production and effects.
Men- the adrenal contribution to androgen production is very small.
