Adrenal cortex Flashcards
Which zone is responsible for synthesising mineralcorticoids
Zona glomerulosa
Name a mineralcorticoid
Aldosterone
The zona fasciculata synthesises what?
Glucocortoids (cortisol)
What does the zona reticularis synthesis?
Androgens
What is the precursor of steroid hormones?
Cholesterol
The synthesis of sex hormones stops at which point in the adrenal cortex?
Stops at androgen. Then in gonads the androgen is converted to estrogen and testosterone
11 Beta hydroxylase catalyses which reaction?
Cortisone / deoxycortisol into hydrocortisone
Where is CRH released from and where does it act on?
Released from hypothalamus and acts on anterior pituitary
What is CRH
Corticotrophin releasing hormone
When CRH acts on the anterior pituitary, what happens?
Adrenocorticotrophic hormone(ACTH) is released
Where does ACTH bind to and what effect does it have?
Binds to adrenal cortex to stimulate the production of cortisol.
How does ACTH regulate cortisol synthesis?
The conversion of cholesterol into pregnenolone is controlled by ACTH which is the first step in the synthesis pathway.
It does this by changing the gene expression of the enzyme in the cortex that catalyses this reaction
ACTH has no effect on which region of the adrenal cortex?
Zona glomerulosa
true or false, ACTH has no effect on cholesterol update and synthesis?
False. ACTH increases cholesterol uptake and synthesis
What is the enzyme that converts cholesterol into pregnenolone?
Cholesterolesterase
What impact does ACTH have on the cells of the adrenal cortex?
Because it is a trophic hormone, it increases the size and functionality and number of the cells. No ACTH = atrophy of adrenal gland
Why is there a large surge of cortisol upon waking the morning?
Helps to mobilise your nutrients to use for energy after fasting for so long during sleep
Is cortisol anabolic or catabolic?
Catabolic. Needs to breakdown muscle and fat to release protein (amino acids) into circulation
Why is it so important to stabilise glucose levels during times of stress?
To fuel the brain, since it cannot store its own glycogen.
List 2 potential causes of Cushing’s syndrome
ACTH secreting tumour
Adrenal tumour
Over medication of anti-inflammatory steroids
List 3 Sx of Cushing’s syndrome
Poor healing / immunity Thin skin and hair Body fat redistribution (buffalo hump, abdominal fat) Protein depletion Insulin resistant diabetes
The drug used to treat Cushing’s syndrome is?
Metyrapone
Explain metyrapone MOA.
Inhibits 11-B hydroxylase which inhibits glucocorticoid synthesis
Name 2 exogenous glucocorticoids
Prednisolone
Hydrocortisone
Budesonide
Name an exogenous mineralcorticoid
Fludrocortisone
Describe how aldosterone regulates fluid.
It promotes sodium retention (increasing reabsorption of water) and increases potassium excretion.
How would low aldosterone cause death?
Thick blood due to too much water excretion would lead to circulatory shock.
Addison’s disease, chronic failure of the adrenal cortex, is treated with what?
Exogenous glucocorticoids and mineralcorticoids
Define HPA
Hypothamus-pituitary-adrenal axis
The rate limiting step of the conversion pathway is…
ACTH
Why are corticosteroids only produced as they are needed?
Because they cannot be stored in vesicles since they are too lipophillic
List some examples of a stressful event that can trigger the release of cortisol
Exams, hypoglycaemia, starvation, infection, trauma, etc
What are the two physiological regulatory mechanisms that stimulate cortisol release
Circadian rhythm (surge upon waking) Stress (stressful events throughout the day)
Cortisol causes muscle anabolism. True or false.
False. Cortisol has a catabolic effect on muscles. Goal is to breakdown muscles to release amino acids which can be turned into glucose. Main role of cortisol is to stabilise glucose levels
3 causes of Cushing’s syndrome
ACTH secreting tumour
Adrenal tumour
Over medication with steroid medications
3 symptoms of Cushing’s syndrome?
- thin hair and skin
- poor healing and immunity
- body fat redistribution (buffalo hump)
Compare hydrocortisone and prednisolone
Hydrocortisone is exogenous cortisol, and has the same receptor affinity, so it used as replacement therapy. Prednisolone has a high affinity for the anti-inflammatory receptor, so it used as an anti inflammatory.
What stimulates the release of aldosterone
Low BP
low ECF
low sodium levels
High potassium levels
Role of aldosterone in kidneys?
Promote sodium retention (and therefore water retention) and increases potassium excretion.
Short term and long term consequences of aldosterone deficiency?
Short = electrolyte imbalances and dehydration and hypotension
Long term = circulatory shock
Addison’s disease cause?
Autoimmune or chronic gland failure
Addison’s disease treatment?
Replacement glucocorticoids (hydrocortisone) and mineralocorticoids (fludrocortisone)
Which zone is the outermost and which is the innermost?
Outer = zona glomerulosa Middle = zona fasciculata Inner = zona reticularis
First step of synthesis pathway for all steroid hormones?
Cholesterol to pregnenolone
What is the purpose of cortisol breaking down muscles into amino acids?
Because the amino acids can be used in gluconeogenesis to create more glucose
What is the purpose of cortisol inducing lipolysis?
Lipolysis breaks down far until fatty acids, that can be used as an alternative to glucose for energy. This spares glucose to be used in the brain
Prolonged suppression of the HPA axis using glucorticoids can lead to what?
Irreversible atrophy of the adrenal gland (zona fasciculata)
ACTH deficiency would NOT decrease the production of which hormone?
Aldosterone
Define Addison’s disease
Adrenal hyposecretion.
Sx of cortisol deficiency
Low blood glucose, poor response to stress
Sx of aldosterone deficiency
Low BP, hyperkalemia (high Potassium which can affect cardiac rhythm) and hyponatremia (low sodium, which reduces ECF volume and therefore causes low BP)
