Glucocorticoids/corticosteroids Flashcards
What are the two types of corticosteroids? And where are they made and released from?
Glucocorticoids and mineralocorticoids are made and released from the adrenal cortex and it’s often termed the salt and sugar hormone
What does glucocorticoids do?
They are known as the sugar hormones, they are responsible for sugar, carbohydrate and protein metabolism. They are also potent anti inflammatory agents and acts as a immunosuppressant.
So it promotes metabolism, maintain blood sugar levels via gluconeogenesis and glycogen synthesis. It also maintains blood pressure and provide resistance to stress. It also plays a part in fluid balance in the body.
What do mineralocorticoids do?
They are known as the salt hormone and control electrolyte and water in the kidney.
What cause cortisol to be released?
Stress activate the release of COrtisol releasing hormone CRH from the paraventricular nucleus of the hypothalamus on the anterior pituitary gland causing it to release ACTH adrenal cortico tropic hormone which acts on the adrenal gland to release cortisol
What cause aldosterone to be released?
Aldosterone is released when there is a decrease in sodium or increase in potassium level in the blood. Decrease in electrolyte affects blood volume, drop in blood volume/BP signals the kidney to initiate the angiotensin cascade which is a potent vasoconstrictor.
High levels of cortisol has effect on he release of aldosterone as well. They can interact with specific receptors to activate aldosterone release.
Does cortisol have a long half life.
No it have a short half life and gets broken down very very quickly to cortisone.
What can stop aldosterone release?
When there is an increase in blood pressure or blood volume, the heart release atrial natriuretic peptide which have an inhibitory effect on the zona glomerulosa of the adrenal cortex. Decreasing aldosterone release.
What happens when zona glomerulosa of adrenal cortex is stimulated?
It will have increased secretion of aldosterone which target kidney tubules to increase absorption of NA and water and increase K excretion. This in turn increase blood volume and blood pressure
What does the metabolic actions of glucocorticoids involve?
It involves the breakdown of protein and fats (muscle wasting), decrease glucose usage and increase gluconeogenesis. It have a tendency to cause hyperglycaemia and thus increase glycogen storage.
How does glucocorticoids have hormone regulation?
It have the ability to produce negative feedback on both the hypothalamus and pituitary gland
What are glucocorticoids cardiovascular effects?
It can decrease microvascular permeability and cause vasodilation
How does glucocorticoids affect the CNS?
It cause mood changes and is linked with memory change due to stress.
How does cortisol prepare the body for he fight or flight response?
Cortisol flood the body with fight or flight response by flooding the body with glucose, supplying an immediate energy source to large muscles.
Cortisol inhibits insulin production in an attempt to prevent glucose from being stored so it is used immediately. Cortisol also encourage the synthesis and storage of glycogen.
What are the anti inflammatory effects of glucocorticoids?
Glucocorticoids decrease microvascular exudate on so it decrease the influx of cells to an site of inflammation.
Glucocorticoids decrease inflammatory mediators and cytokines which decrease expression of COX2, this in turn reduce levels of eicosanoids and decrease levels of cytokines and complement levels
Glucocorticoids decease function of inflammatory effector cells which inhibit cell migration and mediator release, this reduces clonal expansion of B cells and T cells. There will be reduction in chronic inflammatory events and NB healing and repair is inhibited.
How does glucocorticoids decrease gene expression?
Glucocorticoids first enters the cell through passive diffusion then bind to GCreceptor and dissociate Heat shock protein, this cause the receptor hormone complex to translocation to the nucleus which then increase or decrease end expression.
Genetic changes invoices increased hepatic gluconeogenesis, increase pupil hairs, muscle catabolism and inhibition of peripheral glucose uptake in muscle and adipose tissue.
How does glucocorticoids switch gene expression on/off?
Glucocorticoids interacts with receptor with promoter regions, these promoter regions have glucocorticoid response elements (GREs) and occupation of these elements turn on/off certain genes.
Steroid/receptor complexes are known to prevent gene activation from other methods such as transcription factors, how does it do this?
Glucocorticoids can induce inhibitor kappa B alpha which inhibits transcription actors that is involved in switching on COX 2 such as NFkappaB
Dexamethasone is a glucocorticoid agonist, how does it work?
Unbound dexamethasone can cross cell membranes and binds with high affinity to specific cytoplasmic receptors, this result in a modification of transcription and protein synthesis to reduce inflammation.
How is dexamethasone inhibitory?
It involve pospholipase A2 inhibitory proteins, lipocortins which control biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes.
It’s central action is induction of inhibitor kappa B alpha and inhibits NF kappa B.
What are therapeutic uses of glucocorticoids?
It can be used to treat Addison’s disease by treating adrenal insufficiency or failure, treatment require a combined GC and MC.
It can be used to treat inflammation for asthma l, rhinitis, skin disorder, sports injuries and reduction of cerebral oedema in patients with brain tumours
It can by used as immunosuppressants such as inhibiting graft and host reactions in tissue transplant
What are examples in glucocorticoids?
Hydrocortisone, pres isolate, dexamethasone and betamethasone
Effects of glucocorticoids compared to NSAIDs
Glucocorticoids inhibit the production of arachidonic acid as well as expression of Cox 2 where as NSAIDs only decrease activity of Cox 2
What is aldosterone?
Aldosterone is an endogenous mineralocorticoids and its secretion is controlled by renin-angiotensin system and ACTH.
How does mineralocorticoids increase sodium retention in the distal tubules?
It stimulate Na/H exchanger via aldosterone receptors
It enters cells and up regulate na permeability via endothelium sodium channels in cell membranes
It enters cell and stimulate upregulation of basil atrial na/K appease pump
It also cause water retention and loss of potassium and H.
