Basic Andrenal Gland Physiology Flashcards
define permissive actions
when the presence of one hormone is required in order for another hormone to exert its full effects on a target cell.
explain the structure of the adrenal glands
what are the 3 zonas and what are their functions?
how are adrenal hormone productions altered?
explain the Corticosteroid Mechanism
- Corticosteroids are lipid-soluble - pass through cell surface membrane
- They bind to specific intracellular receptors
- Pass through nuclear membrane
- Then cause a direct action (alter gene transcription) by the receptor binding to hormone response element (e.g. glucocorticoid response element).
- They can also recruit coactivators which further stimulate transcription of the gene
what are glucocorticoids?
Synthesised in zona fasciculata
Responsible for regulation of sugar in our body
Essential to life
They are Important in homeostasis e.g. conditioning the body’s response to stress
Have actions on most of the tissues and organs in our body
Some of their actions are permissive - do not directly initiate an action but allows the action of other hormones to occur i.e. allow the effects of catecholamines on vascular tone
Permissive actions are only apparent if there is a deficiency of the initial hormone.
what is the action of glucocorticoids?
The following actions are important in times of stress
Increase glucose mobilisation
stimulates gluconeogenesis
stimulate amino acid generation
increased lipolysis
Maintenance of blood circulation
Regulation of vascular tone
Control salt & water balance
Immunomodulation
They dampen the immune system response
how are glucocorticoids transported?
clinically, what is measured?
Most are bound to corticosteroid-binding globulins (CBG) - approx. 90%
Some are bound to albumin - approx. 5%
some free - approx. 5%
only free glucocorticoids are able to cause an effect
Clinically: the total cortisol is measured and not just free level
↓ CBG levels during an inflammation indicate increased free cortisol levels
when does cortisol bind?
Non-stressed state: lots of cortisol is bound to CBG - most remains in BV - Only free cortisol is able to enter cell cytoplasm.
Stressed state (i.e. sepsis, infection): CBG cleaved - increased amount of free cortisol (little bound to CBG) - more movement out of BVs into cell cytoplasm.
how is cortisol regulated?
- Stressors (e.g. hypoglycaemia, hypotension, infection, surgery) and Circadian rhythm stimulate the release of neurotransmitters which stimulate the production and release of CRH
- CRH stimulates ACTH release which then stimulates release of cortisol at the adrenal cortex.
- Circulating Cortisol then has its effects on tissue action but also gives -ve feedback on CRH & ACTH by binding to glucocorticoid receptors in pituitary and hypothalamus - which inhibit their production.
what is the effect of ACTH on adrenal size?
Low ACTH –> small adrenal size (atrophy)
ACTH excess –> large adrenal glands (adrenal hyperplasia)
what rhythm does cortisol follow?
how?
Circadian - occurs once every 24 hrs
Cortisol levels are low during the night - increase during early morning
peaks around 7-8 am
progressively decreases
smaller peak again after meal time
then progressively decrease again
ACTH mimics release of Cortisol
define stress (in this context)
give examples of stressors that have an effect on cortisol levels
Stress: sum of body’s responses to adverse stimuli
different stressors all have similar effect on cortisol levels e.g:
Infection
Hypotension
Hypoglycaemia
trauma/surgery
haemorrhage
medical illness
psychological response
can be a response to exercise/exhaustion
what is the effect of surgery on cortisol levels?
Effect of general surgery on cortisol levels - massive increase of cortisol during surgery - levels remain high for days after (loss of diurnal variation) - takes a few days for rhythm to normalise.
Levels remain high as -ve feedback is lost - stress cytokines repeatedly stimulate CRH release from hypothalamus
CRH stimulates increase release of ACTH - increase cortisol release
There is also a reduced synthesis and increased breakdown of CBG so increase free cortisol
There is also an increase of cytokines which stimulate local steroid activation at the tissue level.
what are mineral corticoids?
Synthesised in zona glomerulosa (aldosterone synthase present in this region)
Main mineralocorticoids are aldosterone & DOC (deoxycorticosterone)
DOC has 3% of the activity of aldosterone
Mineral corticoids are controlled though the interaction between the kidneys and the adrenal glands - ACTH does not play a main regulatory role
Essential to life
Critical to salt & water balance. Effects occur in:
kidney – most important
colon
pancreas
salivary glands
sweat glands
how are mineral corticoids regulated? (Renin-angiotensin-aldosterone system)
Renin-angiotensin-aldosterone system
Juxtaglomerular cells of kidney produce renin due to reduced renal blood pressure
Renin converts angiotensinogen to angiotensin I in the liver
ACE (angiotensin converting enzyme produced in the lungs) converts angiotensin I to angiotensin II.
Angiotensin II stimulates aldosterone release from adrenal cortex by binding to the AT1 receptors –> This causes Na+ & water retention (and potassium excretion) => increased blood volume => increased BP
Therefore, loss of aldosterone results in lower volume of free fluid.
Only focus on outer circle
what is mineral corticoid receptor specificity?
Both aldosterone and cortisol bind and have equal affinity to the mineral corticoid receptor
Therefore, they both stimulate gene transcription and stimulate the activity of apical Na channel and NaK-ATPase.
Why isn’t MR swamped by cortisol?
Cortisol is more abundant but less binds to MR as 11β-HSD2 enzyme in kidney converts cortisol to cortisone -> cannot bind to MR
Liquorice ingestion inhibits 11β-HSD2 so you get apparent mineralocorticoid excess syndrome (AME) - both leads to excess MR activation by cortisol
what does the adrenal medulla do?
Part of autonomic nervous system, contain neuroendocrine chromaffin cells.
The adrenal medulla acts like a specialised ganglion. It is supplied by sympathetic preganglionic neurons (Ach used as transmitter)
Stimulation causes chromaffin cells to synthesise and release catecholamines (adrenaline & noradrenaline)
Not essential for life
explain catecholamine synthesis
Cortisol has permissive action on catecholamines - high local cortisol levels required for synthesis of catecholamines
More adrenaline produced than noradrenaline (80:20)
Small amounts of dopamine is also produced
The medulla converts tyrosine to catecholamines
Sympathetic stimulation and cortisol induction are required for the stimulation of tyrosine hydroxylase for the conversion of tyrosine to DOPA.
Sympathetic stimulation is required to activate dopamine beta-hydroxylase for the conversion of dopamine to noradrenaline
The conversion of noradrenaline to adrenaline via phenylethanolamine N- methyltransferase requires the presence of cortisol.
what are the different adrenergic receptors that catecholamines act on?
Catecholamines act through different adrenergic receptors.
These are specific for different tissues or organs:
Alpha 1 – present in smooth muscle and stimulates contraction e.g. cause vasoconstriction of blood vessels
Alpha 2- stimulates inhibition of neurotransmitter (noradrenaline) release and causes smooth muscle contraction
β1 – Heart – increases heart rate and contractility
β2 – Smooth muscle relaxation in the bladder, uterus, bronchial and Liver
β3 – Fat cells, cause lipolysis and thermogenesis.
