Session 12 ILOs - The Adrenal glands, RAAS and Adrenal disorders Flashcards
Describe the anatomical division of the adrenal gland in terms of the different layers of the cortex and the relationship between the cortex and medulla
To ask:
Is the androgens the main hormone produced by the zona reticularis?
What are androgens - what is the relationship between androgens, oestrogen and testosterone?
- Capsule protects the adrenal glands
- Cortex is the layer above the medulla but beneath the capsule
- Cortex - contains 3 layers, each producing different hormones (GFR (Glomerular filtration rate), Salt, sugar, sex)
Zona Glomerulosa - produces mineralocorticoids e.g. aldosterone
Zona Fasiculata - produces glucocorticoids e.g. cortisol
Zona Reticularis - produces glucocorticoids + small amounts of androgens (sex hormones which can be converted to oestrogen and testosterone in peripheral tissues) androgens - e.g testerone and oestrogen
Medulla - contains chromaffin cells
Produces Adrenaline (80%) and Noradrenaline (20%)
Describe the difference in origin tissues of different parts of the adrenal gland
Different areas of the adrenal glands arise from different tissues:
Cortex = mesoderm origin
Medulla = neural crest cell origin which subsequently migrate into the developing cortex
Name the hormones produced by the different layers of the adrenal cortex
Cortex:
Zona Glomerulosa - mineralocorticoids e.g. aldosterone
Zona Fasciculata - glucocorticoid e.g. cortisol
Zona Reticularis - produces glucocorticoids + small amounts of androgens (sex hormones which can be converted to oestrogen and testosterone in peripheral tissues)
Medulla (not part of the adrenal cortex)
Adrenaline (80%) - fight or flight response
Noradrenaline (20%) - fight or flight response
What are the functions of mineralocorticoids like aldosterone?
Zona Glomerulosa - mineralocorticoids e.g. aldosterone
- Central role in regulation of plasma Na+, K+ and arterial blood pressure
- Promotes expression of Na+/K+ pump increasing reabsorption of sodium and water back into the blood
- This influences water retention, blood volume & therefore blood pressure
- Central component of renin-angiotensin-aldosterone system (RAAS)
What are the functions of glucocorticoids like cortisol?
Zona Fasciculata - glucocorticoid e.g. cortisol
- Exerts it’s actions by Regulating gene transcription
- Has negative feedback to the hypothalamus to inhibit CRH and ACTH release
- Many actions but main =
- Increased proteolysis in muscle
- Increased lipolysis in fat
- Increased gluconeogenesis in liver
- Anti-inflammatory effects
- Depression of immune response
- Resistance to stress
What are the functions of androgens?
Zona Reticularis - androgens
- Promote axillary and pubic hair growth in both sexes
- In males, DHEA converted to testosterone in testes (after puberty this is insignificant since testes release far more testosterone themselves)
- In females, promote libido and are converted to oestrogens by
other tissues. After menopause this is only source of oestrogens.
Give 2 examples of androgens
- (DHEA) and androstenedione are types of androgens
What are the functions of adrenaline, produced from the medulla?
Medulla
Adrenaline (80%) - fight or flight response
Noradrenaline (20%) - fight or flight response
F or F: (6)
- Increased HR
- Increased contractility
- Increased bronchodilation
- Increased vasodilation (mucles)
- Increased vasoconstriction (skin and GI tract, so it can go to muscles)
- Increased glycolysis in muscles
Describe in general terms the structure and functions of the steroid hormones
And give 5 examples of steroid hormones
- All made from cholesterol in adrenal glands or gonads
- All lipid soluble
Bind to receptors of the nuclear receptor family to modulate gene transcription
• Glucocorticoids
• Mineralocorticoids
• Androgens
• Oestrogens
• Progestins
What are corticosteroids?
Name the 2 kinds
- Corticosteroids are a class of steroid hormones
- Produced in the adrenal cortex or made synthetically. There are two kinds: glucocorticoids and mineralocorticoids
Explain how the steroid hormones affect their target tissues (check discussion board)
Explain how corticosteroids act
- Corticosteroids diffuse across plasma membrane
- Bind to glucocorticoid receptors which causes dissociation of chaperone proteins
- Receptor/ligand complex then translocates to the nucleus
- Dimerisation with other receptors can occur
- Receptors bind to glucocorticoid response elements or other transcription factors
Explain how cortisol secretion is controlled by ACTH and CRH
- Cortisol is controlled by negative feedback of the hypothalamic pituitary adrenal axis
- Low ATCH or CRH would decrease cortisol production whereas increased ATCH or CRH would increase cortisol production
- However, high cortisol would inhibit ATCH or CRH production therefore lowering cortisol levels again
Explain how ACTH can lead to increased pigmentation in certain areas of the body
- Lower levels of ACTH will decrease the level of cortisol
- Decreased cortisol means that there is decreased negative feedback on the anterior pituitary
- So we need to synthesise more acth
- ACTH is made from POMC, so more is POMC required to synthesise ACTH
- However POMC also makes MSH (melanin stimulating hormone) which increases melanin production and therefore hyperpigmentation
Describe the main actions of cortisol
- Exerts it’s actions by Regulating gene transcription
- Negative feedback to the hypothalamus to inhibit CRH and ATCH release
- Increases protein breakdown
- Increased lipolysis in fat
- Gluconeogensis in liver
- Anti-inflammatory effect
- Immune response depression
- Resistance to stress
Describe in general terms the structure and functions of adrenaline
Adrenaline is formed from Tyrosine
Tyrosine -> Levodopa -> Dopamine -> Noradrenaline -> Adrenaline
N-methyltransferase is required to convert Noradrenaline to Adrenaline
Adrenaline binds to adrenergic receptors involved in the sympathetic or fight or flight response to cause:
SEE IMAGE
Explain how adrenaline exerts its effects on cells
Adrenaline binds to adrenergic receptors involved in the sympathetic or fight or flight response
GCPR’s:
G protein : QISS
adrenoreceptor : (a1, a2, b1, b2)
Describe the components and overall function of the renin angiotensin aldosterone system
- The RAAS gets activated when BP or BV drops, so it aims to increase them
Renin is released from granular cells in the juxtaglomerulus apparatus - trigged by:
- Reduced NaCl delivery to distal convoluted tubule
- Reduced perfusion pressure in kidneys
- Sympathetic stimulation of JGA - juxtaglomerulus apparatus
(Indicating low BP)
Renin accelerates the conversion of angiotensinogen to angiotensin I and then ACE - angiotensin converting enzyme - converts angiotensin I to angiotensin II
Angiotensin II acts on angiotensin receptor 1 and 2 (mainly on AT1 receptors) to cause effects at 5 different sites :
1) Arterioles - vasoconstriction
2) Kidneys - Stimulates sodium reabsorption at kidney
3) Sympathetic nervous system - increased release of noradrenaline
4)Hypothalamus - increases thirst sensation to increase ADH release
5) Adrenal cortex - stimulates release of Aldosterone
Aldosterone:
- Central role in regulation of plasma Na+, K+ and arterial blood pressure
- Promotes expression of Na+/K+ pump increasing reabsorption of sodium and water back into the blood
- This influences water retention, blood volume & therefore blood pressure (increased bv and bp)
Explain the effects of over-secretion and under-secretion of cortisol
Over-secretion of cortisol = Addison’s disease (7)
- Weakness
- tiredness
- weight loss
- hypoglycaemia
- increased skin pigmentation
- Postural hypotension
- Annorexia
Under-secretion of cortisol = Cushing’s syndrome
- Cushingoid features ie: (6)
- buffalo hump
- purple striae
- abdominal obesity
- moon-shaped face
- Weight gain
- Hypertension
- Thin,weak arms and legs
Describe tests of adrenal cortical function
- Measurement of plasma cortisol
- ACTH levels
- 24hr urinary excretion of cortisol and its breakdown products (these 3 are important in investigating suspected adrenocortical disease)
- Dynamic function tests may be used in the differential diagnosis of adrenocortical disease:
- Dexamethasone suppression tests
- ACTH stimulation tests
- Dexamethasone (potent synthetic steroid) that (when given orally) normally suppresses secretion of ACTH and thus cortisol
- Low dose Dexamethasone initially to see whether there is any suppression of cortisol at all (to generally confirm Cushing’s syndrome)
- High dose Dexamethasone if there is no suppression on low dose
- Levels of ACTH and cortisol can reveal whether there is Cushing’s disease (caused by a benign pituitary adenoma that secretes ACTH) adrenal Cushing’s (caused by an adrenal tumour producing excess cortisol) or non-pituitary-adrenal tumours producing ACTH and/or CRH (e.g. small cell lung cancer)
Explain how cortisol can have weak mineralocorticoid and androgen effects
At high concentrations, cortisol can have weak mineralocorticoid and androgen effects
- The actions of cortisol on target tissues are mediated by binding to receptors in the cytoplasm/nucleus
- All steroid hormone receptors have similar basic structure with hormone and DNA binding domains
- The hormone binding domains of the mineralocorticoid and androgen receptors have over 60% sequence homology with the hormone-binding domain of the glucocorticoid receptor
- Thus, cortisol can bind to these receptors to a limited extent causing their partial activation
Which adrenal hormone is the most serious to be deficient in? (out of mineralocorticoid, cortisol and androgen)
Cortisol
