Where do you find the adrenal glands?
On top of the kidneys
What is the structure of the adrenal glands and where are they derived from?
Fibrous capsule around entire gland
Cortex (mesoderm origin-envelopes medulla)
-zona glomerulosa (produces mineralocorticoids)
-zona fasiculata (produces glucocorticoids)
-zona reticularis (produces glucocorticoids and some androgens)
Medulla (from neural crest cells)
-chromaffin cells (secrete mostly adrenaline, but also noradrenaline)
What are chromaffin cells?
Post ganglionic neuronal cells with no axon
- usually sympathetic
- secrete NA/A into bloodstream
Give an example of a mineralocorticoid:
Aldosterone
Give some examples of glucocorticoids:
- cortisol (main)
- corticosterone
- cortisone
Give some examples of androgens:
Sex hormones
-dehydroepiandrosterone
-androstenedione
These are converted to testosterone/oestrogen in peripheral tissues
What is the main function of corticosteroids?
Steroid hormones bind to intracellular receptors as they are lipid soluble and affect gene transcription
What are the steroid hormones derived from and where are they synthesised?
Derived from cholesterol
Synthesised in adrenal glands and gonads
Why is the enzyme 21-hydroxylase clinically important?
Deficiency in this causes congenital adrenal hyperplasia
- decreased cortisol and aldosterone= health problems
- increased androgens= early puberty and genital changes
Method of action of corticosteroids:
-readily diffuse across plasma membrane
-bind to glucocorticoid receptors
-binding causes dissociation of chaperone proteins
-receptor ligand complex translocates to nucleus
(dimerisation with other receptors can occur)
-receptors bind to glucocorticoid response elements (GRE’s) or transcription factors
Give an example of a chaperone protein:
Heat shock protein 90
How is aldosterone transported in blood?
Bound to serum albumin (sometimes to transcortin)
What is the role of aldosterone?
Regulation of gene transcription
Regulation of plasma Na+/K+/arterial blood pressure
-acts on collecting duct of nephron to promote expression of Na+/K+ pump
-promoting reabsorption of Na+ and excretion of K+
=influencing water retention, blood volume and therefore BP
(reabsorbing more Na+ causes more water to be reabsorbed)
What is the role of aldosterone inthe renin-angiotensin-aldosterone system? (RAAS)
Angiotensin 2 acts on the adrenal cortex to produce aldosterone when A2 receptors are activated
What are the types of hyperaldosteronism?
Primary: defect in adrenal cortex
- bilateral idiopathic adrenal hyperplasia (most common)
- aldosterone secreting adenoma (Conn’s syndrome)
Secondary: over activity of RAAS
- renin producing tumour
- renal artery stenosis: reduced blood supply stimulates production of renin
How do you distinguish between primary/secondary hyperaldosteronism?
Primary: low renin levels (high aldosterone:renin ratio)
Secondary: high renin levels (low aldosterone:renin ratio)
What are the signs and treatment for hyperaldosteronism?
Signs
- high BP
- left ventricular hypertrophy
- stroke
- hypokalaemia
- hypernatraemia (high calcium)
Treatment:
- aldosterone producing adenomas are removed by surgery
- drug called spironolactone used (mineralcorticoid receptor agonist)
When is cortisol released?
In response to ACTH, released by zona fasiculata
-negative feedback (increased cortisol) to hypoathalmus inhibits CRH/ACTH release
How is cortisol transported?
Bound to carrier protein in plasma called transcortin
What is the action of cortisol?
-increased proteolysis in muscle
-increased lipolysis in fat
(catabolic effects)
-increased gluconeogenesis in liver
-anti-inflammatory effects (useful for allergic reactions as inhibits macrophage activity/mast cell degranulation)
-depression of immune response (given to transplant patients)
Effect of glucocorticoids (cortisol) on metabolism:
Net effects
- increased glucose production
- breakdown of protein
- redistribution of fat (to abdomen, supraclavicular fat pads:buffalo hump, dorso-cervical fat pads: moon face)
- reduced sensitivity to insulin in muscles as cortisol inhibits GLUT4 translocation
- increased glycogen stores in liver
What is Cushing’s syndrome and its causes?
Excessive exposure to cortisol
- prescribed glucocorticoids
- benign pituitary adenoma secreting ACTH (Cushing’s disease)
- excess cortisol produced by adrenal tumour (Adrenal Cushing’s)
- non pituitary-adrenal tumours producing ACTH (small cell lung cancer)
What are the signs and symptoms of Cushing’s syndrome?
- plethoric moon shaped face
- buffalo hump
- abdominal obesity
- purple striae (weakened strength of skin due to proteolysis)
- acute weight gain
- hyperglycaemia
- hypertension
Give some examples of steroid drugs and what they are used to treat:
Prednisolone Dexamethasone -asthma -IBS -RA (inflammatory diseases) -used to supress immune reaction in transplant patients
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Lecture 1 (Alcohol metabolism & Oxidative stress)44
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Lecture 2 (Protein & AA metabolism)7
