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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
-retains water
-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.

Glucocorticoids

-metabolic
-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
DECREASED MEDIATORS:
-glucocorticoids inhibit phopholipase A2
-this blocks production of arachidonic acid, prostaglandins and leukotrienes from cell membrane phospholipid.

Hydrocortisone

-taken orally
-replacement cortisol

Beclomethasone

-inhaled
-asthma

Prednisolone

-taken orally
-inflammatory and

Dexamethasone

-taken orally
-inflammation

Betamethasone

-topically
-skin inflammation

Adverse effects of glucocorticoids include...

-suppression of response to infection
-suppression of synthesis endogenous glucocorticoid
-metabolic effects
-osteoperosis

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.

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