Lecture 27: Stress and the adrenal glands Flashcards
What are three classes of hormones released from the adrenal glands?
- mineralcorticoids
- glucocorticoids
- catecholamines
Where are the adrenal glands?
they are bilateral organs above the kidneys
What two tissues does the adrenal gland derive from?
neural and epithelium
How many structures make up the adrenal gland?
2
What are the names of the structures of the adrenal gland? What percentage of the adrenal gland so these parts make up?
There is the cortex which makes up 80% of the adrenal gland encapsulates the medulla which makes up 20% of the gland
What cells make up the medulla?
chromaffin cells
What is significant about the different zones of the adrenal gland?
they all produce a different hormone
How many zones is the medulla split into?
1
How many hormones does the medulla secrete?
2
What are the two hormones that are secreted by the medulla?
epinephrine
norepinephrine
How many zones is the cortex split into?
4
How many of the 4 zones of the cortex secrete hormones?
3
What are the names of the zones in the cortex (from the outside in)?
capsule
glomerulosa
fasciculata
reticularis
What is the zone in the cortex that doesn’t release hormone?
capsule
What is the name of the hormone secreted from the glomerulosa on the cortex in the adrenal medulla?
aldosterone
What is the name of the hormone secreted from the fasciculata on the cortex in the adrenal medulla?
cortisol
What is the name of the hormone secreted from the reticularis on the cortex in the adrenal medulla?
androgens
What is the precursor to adrenal cortex hormones?
cholesterol
From cholesterol, there is a rate limiting reaction. What is this and what does it form?
There is a side chain cleavage which converts it to pregnenolone.
Can pregnenolone exist for very long?
no
What are the three broad classes of hormones that pregnenolone is converted to?
- glucocorticoids
- mineralocorticoid
- sex steroid precursors
Give two examples of glucocorticoids and where is this located?
cortisol
corticosterone
in the zona fasiculata
Give an example of a mineralocorticoid and where it’s located
aldosterone
in the zona glomerulosa
Give an example of a sex steroid prescursor and where it’s located
androstenedione
in the zona reticularis
What does aldosterone act to do?
it acts to maintain fluid volume
What is the main site of action of aldosterone?
kidneys
How does aldosterone maintain fluid volume?
by increasing the reabsorption of sodium and water and increasing the secretion of potassium
What receptor does aldosterone bind to?
mineralocorticoid receptors (MR)
What is the direct effect of aldosterone increasing the reabsorption of sodium and water and increasing the secretion of potassium?
it increases water retention and increases blood pressure
Describe the cell signalling of aldosterone
Because it is lipophilic, it diffuses into the cell where it binds to the MR. This MR then binds to the DNA to a response element (a promotor) which activates gene transcription of genes then these are converted to proteins
Are all adrenal cortex hormones lipophlic?
yes because they are precursors of cholesterol
Give two examples of the proteins that are synthesised as a result of aldosterone
ENaC (Na+ channel)
Na+/K+ ATPase
What are the two sides of the cells of the kidney collecting duct called?
apical (tubule)
basolateral (interstitium)
What is the effect of aldosterone creating ENaC and Na+/K+ ATPase?
Na+ enters the cell on the apical side and is then pumped out of the basolateral membrane via the Na+/K+ ATPase. This creates an osmolateral gradient so the H20 flows from the apical side (collecting duct) to the basolateral side (the interstitium)
What 4 organs control the production of aldosterone? Is this an indirect or direct affect?
heart
kidney
liver
lungs
this is an indirect affect
As well as the organs, what else controls the release of aldosterone? Is this an indirect or direct affect?
the K+ load
this is a direct affect
Describe how the K+ load controls the release of aldosterone
The aldosterone is produced by the adrenal glad and there is a direct action on this production from the K+ load. This means that an increase in the K+ load increase plasma K+ which increases aldosterone
Describe the steps that allows the kidney, liver and lungs to control aldosterone production
A _______, having ______ ______ and ________ deprivation leads to a _________ in the __ ___ ___ volume. This stimulates the r_________ j________ cells in the kidney to produce _________. The liver releases a___________ and renin stimulates this to be converted into ____________. The lungs produce a __________ __________ which converts ____________ into ________________ and this affects the __________ ___________ and stimulates the production of ______________
A haemorrhage, having upright posture and Na+ deprivation leads to a decrease in the ECF volume. This stimulates the renal juxtaglomerular cells in the kidney to produce renin. The liver releases angiotensinogen and renin stimulates this to be converted into angiotensin |. The lungs produce a converting enzyme which converts angiotensin | into angiotensin || and this affects the adrenal gland and stimulates the production of aldosterone
Describe how the heart controls the release of aldosterone
The heart releases an atrial natriuretic hormone which stops the release of aldosterone from the adrenal gland.
What is the name of the substance that is released from the kidneys and converts angiotensinogen to angiotensin |?
renin
What is the name of the substance released from the liver that is converted to angiotensin | by renin?
angiotensinogen
What is the name of the enzyme released from the lungs that converts angiotensin | to angiotensin ||?
converting enzyme
What is the name of the substance that is converted to angiotensin || via converting enzyme?
angiotensin |
What is the name of the substance that angiotensin | is converted to via converting enzyme?
Angiotensin ||
Where is cortisol released from?
the adrenal gland
Describe the release of cortisol
Corticotropin releasing hormones reside in the paraventricular nucleus of the hypothalamus and then they project to the median eminence and then stimulate the release of adrenocorticotrophic hormone from the anterior pituitary gland. This stimulates the release of glucocorticoids (such as cortisol) from the adrenal gland
Describe the negative feedback of the release of cortisol
cortisol feeds-back to the paraventricular nucleus to prevent the release of ACTH from the anterior pituitary gland and to the hypothalamus to stop the release of corticotropin releasing hormone
What are the only 2 glucocorticoids and what is the only one present in humans?
cortisol
corticosterone
only cortisol is found in humans
ACTH is needed for the release of cortisol and it comes from a precursor. What is its name?
Proopiomelanocortin
Describe the importance of post-translational modifications on the production of ACTH
We have _______ which is transcribed to ______ and then it is converted to a _________ (_________________). On this protein, have encoded several further __________ that then act as _____________. One is ______ and another is γ_______ and β________ so we can see that the precursor makes a lot of different _______ and ________ is one of them. This shows _________-__________ ____________. _________ can be activated by ___________ and ACTH will need to be ______________ because it won’t be there if we don’t have ___________ that _______ it out
We have DNA which is transcribed to mRNA and then is converted into a protein (Proopiomelanocortin). On this protein, we have encoded several further proteins that can then act as hormones. One is ACTH and another is γMSH and β LPH so we can see that the precursor makes a lot of different proteins and ACTH is one of them. This shows post-translational modifications. Hormones can be activated by metabolism and ACTH will need to be activated because it won’t be there if we don’t have enzymes that cleave it out.
Describe the control of cortisol release
- hypothalamic corticotropin releasing hormone stimulates the release of adrenocorticotropic hormone from the anterior pituitary gland (antidiuretic hormone can also cause ACTH secretion)
- ACTH acts through melanocortin MC2 receptors in the adrenal gland which increases P450 side-chain-cleavage (cholesterol cleavage to form cortisol).
- cortisol is released which negatively feedsback to inhibit the release of CRH from the hypothalamus and to stop the release of ACTH from the anterior pituitary gland
What are the main actions of cortisol in the body?
- it stimulates the ______ to generate _________ and to convert ___________ to ____________
- it stimulates the __________ ____________ to release energy by causing a breakdown of __________________ and __________-_________ ______________
- it also causes the ____________ to break down ___________ to ___________ ___________ to be converted to glucose in the ______________
- glucose uptake into the ___________ ___________ is inhibited as the ____________ is inhibited by ____________
- it stimulates the liver to generate glucose (gluconeogenesis) and to convert glycogen to glucose (glycogenolysis)
- it stimulates the adipose tissue to release energy by causing the breakdown of triglycerides to free-fatty acids
- it also causes the muscles to break down protein to amino acids to be converted to glucose in the liver
- glucose uptake into the muscle cells is inhibited as the insulin is inhibited by cortisol
What effect does cortisol have on muscles?
it maintains muscle function and decreases muscle mass
What effect does cortisol have on bones?
it decreases bone formation and increases bone resorption
What effect does cortisol have on the connective tissue?
It decreases the connective tissue so there is less collagen
What effect does cortisol have on the immune response?
it inhibits inflammatory and immune responses
What effect does cortisol have on the heart?
It maintains cardiac ___________, increases _________ tone and decreases ______________ p______________
it maintains cardiac output, increases arteriolar tone, decreases endothelial permeability
What effect does cortisol have on the maturation of the foetus?
it facilitates the maturation of the foetus
What effect does cortisol have on the kidneys?
It increases g__________ f_________ and ___________ ____________ ___________
it increases glomerular filtration and free water clearance
What effect does cortisol have on the brain?
it modulates emotional tone and wakefulness
Where are catecholamines produced in the adrenal gland?
the adrenal medulla (not the cortex)
What are two examples of catecholamines?
epinephrine (adrenaline)
norepinephrine (noradrenaline)
Describe the sympathetics control of the adrenal medulla
The adrenal gland is under sympathetic control of the sympathetic nervous system. The post-ganglionic neurons project to the adrenal gland and release catecholamines.
What are the 4 cardiovascular effects of adrenaline?
- increasing __________ ____________ (by acting on _______ receptors)
- increasing __________ ___________ (by acting on _________ receptors)
- dilating ___________ ____________ around _____________ (by acting on _____________ arterioles)
- by constricting other ____________ (by acting on _____________ receptors)
- increasing cardiac contractility (by acting on β1 receptors)
- increasing heart rate (by acting on β1 receptors)
- dilating smooth muscle around arterioles (by acting on β2 arterioles)
- by constricting other arterioles (by acting on α1 receptors)
What is the main effect of adrenaline?
to shunt blood to exercising muscles and the brain and away from other tissues
What are the metabolic effects of adrenaline?
- it stimulates the production of _____________ and the conversion of _____________ to ____________ in the ___________
- it inhibits the action of ___________ so glucose is not taken up by the __________ or _________ cells
- it stimulates ____________ breakdown in the muscle and _________ ___________ up-take by the __________
- it stimulates the release of __________ __________ _____________ from the __________ tissue
- it stimulates the release of _______________ from the liver
- it stimulates the production of glucose (gluconeogenesis) and the conversion of glycogen to glucose (glycogenolysis) in the liver
- it inhibits the action of insulin so glucose is not taken up by the muscle or fat cells
- it stimulates glycogen breakdown in the muscle and lactic acid up-take by the liver
- it stimulates the release of free fatty acids from the adipose tissue
- it stimulates the release of ketoacids from the liver
What is stress?
the sum of the biological reactions to any adverse stimulus, physical, mental or emotional, internal or external, that disturbs homeostasis
Which is faster acting, adrenaline or cortisol?
They both have metabolic affects (which are relatively slow) but adrenaline is faster acting because it gets blood to the areas where it is needed
Which hormone’s main effect is vascular changes?
adrenaline
Which hormone’s main effect is metabolic changes?
cortisol
What two things happen in the fight-or flight-response?
adrenal cortex releases cortisol for energy mobilisation and the adrenal medulla releases adrenaline for vascular changes
Chronic stress increases cortisol. What is the effect of this?
- Decreases __________ function
- increases risk of _________ and ____________
- worsens ____________ due to anti-insulin effects
- possibly increases __________ death rate
- might enhance _____________ and ____________ (increased blood lipids, increased cardiac work)
- decreased ________ density
- i__________
- Decreases immune function
- increases risk of infection and cancer
- worsens diabetes due to anti-insulin effects
- possibly increases neuronal death rate
- might enhance artherosclerosis and hypertension (increased blood lipids, increased cardiac work)
- decreased bone density
- infertility
What is Cushing’s syndrome?
Where there is an overproduction of cortisol which causes lots of abdominal fat and means you are prone to cancer, bruises and infections
