The Adrenal Hormones
|Which hormones are released by the adrenal cortex?||cortisol (glucocorticoids), testosterone, aldosterone (mineralocorticoids). (steroid hormones)|
|Which hormones are released by the adrenal medulla?||epinephrine and norepinephrine. (catecholamines)|
|Adrenocortical hormones|| -mineralocorticoids and glucocortocoids (aldosterone and cortisol)|
-act on intracellular nuclear receptors
-receptor plus hormone unfolds and binds to DNA at HORMONE RESPONSE ELEMENTS-leads to transcription of genes
-increases RNA polymerase activity and production of specific mRNAs
-increases protein synthesis
|Nuclear Receptors||Receptors for lipophilic hormones - function within the cell nucleus to activate genetic transcription (production of mRNA). Must be activated by binding to its hormone ligand before it can bind to a specific region of DNA.|
|Which drugs activate nuclear receptors?|| • Oestrogen Receptor Agonists - for hormone|
replacement therapy in postmenopausal women
• Glucocorticoid Receptor Agonist - for inflammation
|Which drugs antagonize nuclear receptors?|| -SPIRONOLACTONE. mineralocorticoid receptor antagonists-for oedema due to liver cirrhosis and for heart failure. |
-TAMOXIFEN. oestrogen receptor antagonists-for prevention and treatment of breast cancer.
-BICALUTAMIDE/CASODEX. androgen receptor antagonists-treatment of prostrate cancer.
|Aldosterone (mineralocorticoids)||-aids in regulating electrolytes and water balance.|
-retain Na in exchange for K
-production mainly regulated by renin/angiotensin system.
-aldosterone antagonist-spironolactone-used as a K sparing diuretic.
-aldosterone acts on distal renal tubes to increase Na reabsorption and increased excretion of K and H.
-aldosterone nuclear receptors occur only in kidneys.
-spironolactone is a competitive antagonist of aldosterone at these receptors.
-the effect of the aldosterone-receptor complex interaction with DNA is to increase the number of Na channels in the membrane of the renal cell.
-negative feedback on anterior pituitary/hypothalamus
-anti-inflammatory and immunosuppressive effects
|Glucocorticoids (metabolic actions)|| -CBH decreased uptake of glucose but increased breakdown of protein to glucose-HYPERGLYCAEMIA |
-Proteins increased breakdown and reduced synthesis
-Fat increased breakdown, redistribution
-Raise plasma glucose levels to provide energy to combat stress.
|Glucocorticoids (anti-inflammatory and immunosuppressive effects)|| REDUCE:|
-blood vessel dilation/leakage
-production of mediators
-inflammatory and immune cell activity
-glucocorticoids inhibit phopholipase A2
-this blocks production of arachidonic acid, prostaglandins and leukotrienes from cell membrane phospholipid.
|Hydrocortisone|| -taken orally|
|Prednisolone|| -taken orally|
|Dexamethasone|| -taken orally|
|Adverse effects of glucocorticoids include...|| -suppression of response to infection|
-suppression of synthesis endogenous glucocorticoid
|Catecholamines (adrenal medulla hormones)||-adrenaline and noradrenaline (to a lesser extent) secreted in response to the sympathetic nervous system (fight or flight)|
-Stimulation releases glucose from the liver and fatty acids from adipose tissue
-actions of epinephrine (adrenaline) in these tissues are mediated by elevations in cyclic AMP levels.
-also maintain BP through ionotropic effects on the heart and vasoconstrictor actions
-people with hypertension can be treated with beta-adrenoreceptor antagonists to reduce cardiac rate
-failure of adrenal medulla is rare but causes hypotension
-tumours of adrenal medulla secrete catecholamines causing hypertension and must be removed surgically.