The Adrenal Hormones Flashcards
Where is the adrenal gland?
On top of the kidneys
Triangle shape
What is the adrenal gland made up of?
Adrenal cortex
Adrenal medulla
What does the adrenal gland do?
Secrete different types of hormones
What type of compounds do the adrenal cortex secrete?
Steroid compounds
Give some examples of the steroid compounds produced by the adrenal cortex?
Glucocoticoids e.g. cortisol
Mineralocorticoids e.g. aldosterone
Sex hormones e.g. testosterone
What type of compounds do the adrenal medulla secrete?
Catecholamines
Give some examples of the catecholamines produced by the adrenal medulla?
Epinephrine (adrenaline)
Norepinephrine (noradrenaline)
What happens in zone glomerulosa in the adrenal cortex ?
Secretion of aldosterone
What happens in zone fasiculata and reticularis?
cortisol
adrenal androgens
What does the adrenal medulla secrete in response to sympathetic nerve stimulation?
Adr and to a lesser extent NA
What does the adrenal medulla secrete in response to?
Stress preparing for “fight or flight”
Priming the body for intense physical activity
What does the adrenal medulla stimulate release of?
Metabolic “fuels”
Glucose from the liver
Fatty acids from adipose tissue
What are the actions of Adr in these tissues mediated by?
Elevations in cyclic AMP levels
How do Adr and NA maintain blood pressure?
Ionotropic effects on the heart (increases heart rate) and vasoconstrictor (contracts blood vessels)
How are people with hypertension treated?
Beta-adrenoceptor antagonists (‘beta blockers’) to reduce HR
What does failure of the adrenal medulla cause?
Hypotension
What is hypotension?
Low blood pressure
What is hypertension?
High blood pressure
What are examples of tumours of the adrenal medulla?
Pheochromocytoma or neuroblastoma
What do tumours of the adrenal medulla cause?
Secretion of catecholamines causing hypertension and must be removed by surgery
What are adrenocortical hormones?
Steroid hormones
What is adrenocortical hormones structure based on?
Cholestrol
What are exampels of adrenal Corticosteroids?
Mineralocorticoids- aldosterone
Glucocotortoids- Cortisol
Sex hormone- androgens
What do adrenal Corticosteroids act on?
Intracellular nuclear receptors
What leads to the transcription of genes?
Receptor plus hormone unfolds and binds to DNA hormone response elements
What does the receptor plus hormone unfold and bind to?
DNA at HRB (Hormones Response Elements)
What does the receptor hormone complex do once bound to DNA?
Increases RNA polymerase activity
Increase production of specific mRNAs
Increases protein synthesis
What are nuclear (or cytoplasmic) receptors?
Soluble proteins localised within the cytoplasm or the nucleoplasm
What does the nuclear receptor have to pass through?
Plasma membrane
Usually by passive diffusion
What are the typical ligand?
Lipophilic hormones, with steroid hormones (e.g. testosterone, progesterone and cortisol) and derivatives of vitamin A and D among them
What happens when the ligand is binding?
Nuclear receptors pass through the nuclear membrane into the nucleus genes activity
What are specific Hormone Responsive Elements (HREs)?
A short sequence of DNA within the promoter of a gene that is able to bind a specific hormone receptor complex and therefore regulate transcription
What happens when ligands bind to receptors which unfold?
Bind receptor binds to DNA
RN polymerase activity increases
Specific mRNA is produced within minutes
Protein synthesis- effects in hours to days
How does Oestrogen Receptor Agonists activate nuclear receptors?
For hormone replacement therapy in postmenopausal women (conjugated equine oestrogens)
What is glucocorticoid receptor agonist for?
For inflammation (hydrocortisone,; dexamethasone)
What is mineralocorticoid receptor antagonist for?
For oedema due to liver cirrhosis and for heart failure (spironolactone)
What are oestrogen receptor antagonists?
For the prevention and treatment of breast cancer (tamoxifen)
What are androgen receptor antagonists?
Treatment of prostate cancer (Bicalutamide/Casodex)
What are agonists?
Agonist drugs mimic the effects of neurotransmitters naturally found in the human brain
What are antagonists?
In contrast to agonist drugs which bind to the neurotransmitters in the brain, antagonist drugs do the opposite: they block the brain’s neurotransmitters
What does aldosterone do?
Regulate salt and water metabolism
Retains Na+ in exchange for K+
Retains water
What is the production of aldosterone regulated by?
Renin/Angiotensin system
What is the aldosterone antagonist?
Spironolactone- used as a Potassium sparing diuretic
What does aldosterone act on?
Distal renal tubules to increase Na+ reabsorption and concomitantly, increased excretion of K+ and H+
Where are aldosterone nuclear receptors?
Only occur in the kidneys
What is spironolactone?
Competitive antagonist of aldosterone at these receptors
What’s the effect of interaction of the aldosterone?
Receptor complex with DNA is to increase the number of Na+ channels in the membrane of the renal cell
What are the three main actions of glucocorticoids?
Metabolic
Negative feed-back on anterior pituitary and hypothalamus
Anti-inflammatory and immunosuppressive effects
What are the metabolic actions of glucocorticoids?
Carbohydrates- decreased uptake of glucose, increased protein breakdown to glucose- hyperglycaemia
Proteins- increased breakdown, reduced synthesis
Fat- increased breakdown, redistribution
What is used to combat stress?
Raise plasma glucose levels to provide energy
What does the anti-inflammatory and immunosuppressive activity reduce?
Blood vessel dilation and leakage
Production of mediators
Inflammatory/ immune cells activity
What is anti-inflammatory and immunosuppressive activity?
Glucocorticoids inhibit Phospholipase A2
This block production of Arachidonic Acid, Prostaglandins and Leukotrienes from cell membrane phospholipid
When is suppression of inflammation and immune response?
Asthma Allergic responses Autoimmune disease Inflammatory conditions Organ transplant Cancer therapy
What are the adverse effects of glucocorticoids?
Suppression of response to infection Suppression of endogenous glucocorticoid synthesis Metabolic effects Osteoporosis Cushing’s syndrome
