The adrenals and their hormones Flashcards
Where does the left adrenal vien drain into?
Renal vien
Where does the right adrenal vein drain into?
Inferior Vena Cava
How many veins do both adrenal glands have?
1
Has 1 vein and many arteries
List the zones of the adrenal cortex and recall the products of the adrenal cortex and medulla
List the zones of the adrenal cortex?
What does the adrenal medulla produce?
Catecholamines
What type of hormones does the adrenal cortex produce?
Corticosteriods
All the blood diffuses down the cortex into the medulla. As the corticosteriods diffuse down the cortex into the medulla it eventually reaches the central vien. The Corticosteriods have a beneficial effect on promoting adrenaline and noraadrenaline production
What cells in the adrenal medulla produce Catecholamines?
Chromaffin Cells
80%-Adrenaline
20%-Noradrenaline
Evens produces a small amount of dopamine
List the types of Corticosteriods produced by the adenal cortex and give examples of each?
Mineralocorticoids-Aldosterone
Glucocorticoids- Cortisol
What other hormones besides Mineralocorticoids and Glucocorticoids can the adrenal cortex produce?
Sex steriods
Androgens and Oestrogens
What zone or zones in the adrenal cortex produces Aldosterone?
Zona Glomerulosa
What zone is Cortisol and Androgens produced in?
Zona Fasciculata
Zona Reticularis
Why are the adrenal cortex hormones also known as C21 steriods
21 Carbons in Mineralcorticoids and Glucocorticoids
Cholesterol has 27 carbons
State the steps for synthesis of genral steriod hormones
LDLs are delivered to the cell and are stored as Fatty Acid Esters (seen as fat droplets)
To synthesise steroid hormones you need to break down the fatty acid esters to liberate cholesterol
Esterase enzymes break down the fatty acid esters
STEROID HORMONES ARE MADE IN THE MITOCHONDRIA
Cholesterol gets into the mitochondrion via StAR Proteins (Steroidogenic Acute Regulatory Protein)
This is one of the rate limiting steps in steroid hormone production
The more StAR proteins you have, the more cholesterol you can get into the mitochondrion and the more steroid hormone you can produce
When cholesterol enters the mitochondrion, there are lots of enzymes that allows the step-wise conversion of the cholesterol into the steroid hormone of choice
The enzymes present in certain cells determines the final steroid hormone product (e.g. adrenal cortical cells have a set of enzymes that produced cortisol)
Recall the synthesis for Cortisol?
Sequence of addition and subtraction
List the steps for aldosterone synthesis?
NO P450c17 ENZYME
Recall the steps for sex hormone synthesis in the adrenal cortex
NO need to remember enzymes
Remember some important intermediate molecules
What is the difference between glomerulosa and the FASCICULATA?
NO p450c17 in glomerulosa
Glomerulosa has Aldosterine synthase
What proportion of aldosterone is free, bound to CBG ( corticosteroid-binding globulin) or bound to Albumin?
40% free
15%- CBG
45%- Albumin
What proportion of Cortisol is free, bound to CBG ( corticosteroid-binding globulin) or bound to Albumin?
10%- Free
80%- CBG
10%- Albumin
Test: Cortisol binds to the glucocorticoid receptor (GR) whereas aldosterone binds to the mineralocorticoid receptor (MR).
Only free unbound hormone can access tissues and bind to relevant receptors.
Is a 5% displacement of hormone (cortisol/aldosterone) from binding proteins going to cause a greater increase in % GR binding or MR binding?
Cortisol
By how much is there a difference in the concentrations of Cortisol and Aldosterone?
1000 x
What is the name of the receptor or receptors that cortisol can bind to?
Glucocorticoid Receptor
Aldosterone Receptor (MR)
What is the major implication of the data below?
Cortisol can bind to and aggrevates the MR just as effectively as Aldosterone and is 1000x more. So what is the point of aldosterone. There is certain tissue that excludes cortisol by making it inactive :11b-hydroxysteriod dehydrogenase 2. So aldosetrone is needed because in certain tissue aldesterone can bind to MR receptor whilst cortisol can’t. An example of this tissue is the kidney- This is the target organ for aldosterone and cortisol cant enter the kidney unless it has very high concentration. The 11b-hydroxysteriod dehydrogenase 2 is found in such tissuess. This enzyme is also in the placenta to prevent maternal cortisol for reaching the baby because cortisol is growth inhibitory.
What 3 things causes renin release?
RENIN IS AN ENZYME
-Decreased renal perfusion pressure (normally associated with decreased arteriole blood pressure) -
Increased renal sympathetic activity- flight or fight response
- The JGA (juxta-glomerular apparatus) has sympathetic innervation
- The sympathetic system is activated when the blood pressure falls
- This leads to renin release
Decreased Na+ load dilivered to the distal tube -This load is measured by the macula densa (Na+ sensor) of the juxtaglomerular apparatus. Sodium diffuses out of the macula cells causing them to shrink which causes Renin production.
Decreased sodium concentration at the top of the loop of Henle
This leads to activation of JGA and the release of renin
Draw a diagram showing the renin angiotensin system?
What does Angiotensin II stimulate?
ANGIOTENSIN II stimulates the zona glomerulosa to produce aldosterone
Low Na+ in blood and high K+ in blood stimulates aldosterone production- not as much as angiotensin II
Draw the Adrenal gland – hypothalamo-pituitary-adrenocortical axis
A key stmuli for cortisol production is Stress- any stress
Describe your cortisol levels throughout the day
Higher when sleeping
Where are the target cells for aldosterone located
target cells for aldosterone are located in the distal tubule and cortical collecting duct,
What are the actions of aldosterone?
Stimulates Na+ reabsorption in the distal convoluted tubule and cortical collecting duct
This is particularly important in the kidneys but is also important in sweat glands, gastric glands and colon)
Stimulates K+ and H+ secretion in the distal convoluted tubule and cortical collecting duct
So it will have an effect on pH regulation of the blood
Draw a diagram shoing the effects of aldosterone inside a cell
What is cortisol mechanism of action inside a cell?
Draw a diagram
For normal physiological effects of cortisol, what ratio of MR to GR receptor stimulation do you need?
Maximal MR stimulation ( MR most important for normal cortisol physiollogical response) excluding the tissue with enzyme protection and Little stimulation of GR
What effects on the body does very high levels and low levels of cortisol have on the body ( chronic- for a long time )?
List 9 for each
When you are stressed, what happens to the proportion of GR to MR stimulation?
The are both highlt stimulated
GR drives your stress response
What effects does cortisol have in the liver?
Stimulate Glycolysis
Stimulate Gluconeogenesis
Increase blood glucose conc
What effect does cortisol have on skeletal muscle and adipose cells?
Decreases bloodflow to skeletal muscle and Fat
Decrase the transporters that causes glucose to enter the cells
CORTISOL WANTS TO INCREASE BLOOD GLUCOSE CONCENTRATION
What effect does cortsiol have on memory function?
Dantate Gyrus- large pink, green and yellow area- important area
Seratonin and cortisol in the hippocampus work together
Seratonin promotes granular cell (have a role in memory formation) proliferation
Cortisol increases the sensitivity of the hippocampus to seratonin
Acute stress response- help with memory- that is why most of your first memories are stressful
What effects does high conc of cortisol like substances have?
If you use high dose of cortisol like substances it has a powerful anti-inflammatory and immunosuppressive efffects
At normal physiological levels it supports the immune system- more research is needed in this level
That is why during exam period you are more likely to get ill
What effect does alcohol and caffine have on cortisol production?
Caffine and Alcohol increase cortisol
Alcohol is more powerful then caffine
If you are chronically stressed how does it effect memory?
Memory gets much worse due to GR receptor having the main effect and bring the major activator.
Example of this is PTSD
Test: What effect would supraphysiological levels of cortisol
have on blood pressure?
Hint – 11 beta HSD II
Normally you have the enzyme barrier in the kidney- high levels can pass the enzyme barrier and has the same effect as aldosteron whilst in the kidney- this causes an increase in blood pressure?
In which zone is Adrenal androgens synthesised?
Zona reticularis
Dehydroepiandrosterone (DHEA)
This is a very weak androgen
Precursor for androgens and oestrogens
Converted to active hormones within target cells (which have appropriate enzymes)
Peak serum levels at 20-30 years, then decreasing steadily with increasing age
Particularly important in post-menopausal women as a precursor for oestrogen (and androgen) synthesis by target tissue in the absence of ovarian steroids
What effects on the body does angiotensin 2 have?
Potent vasoconstrictor
