Adrenal Hormones Flashcards
What are the two regions of the adrenal gland called?
The adrenal cortex and the adrenal medulla
What can the adrenal cortex be divided into?
The outer layer is the zona glomerulosa, the layer under that is the zona fasicialata and the final layer is the zona reticularis
What is the adrenal medulla responsible for secreting?
Adrenaline and noradrenaline (catechloamines)
What is the adrenal cortex responsible for secreting?
The adrenal hormones (steriods)
What does the zona glomerulosa secrete?
Aldosterone
What does the zona fasiculata and the zona reticularis secrete?
Cortisol and androgens (e.g. testosterone)
Where is the adrenal gland found in the body and why is it situated there?
At the back of the body above the kidneys; is positioned there because the hormones it produces can regulate salt concentration of the blood and therefore kidney function
What are the catechloamines and what is there structure?
Adrenaline and noradrenaline and noradrenaline is adrenaline with an extra methyl
What causes the adrenal medulla to secrete catechloamines?
Sympathic nerve stimulation
What does the secretion of catechloamines to in times of stress?
Increases release of metabolic fuels i.e. glucose from the liver and fatty acids from adipose
What other effects do catechloamines have?
They have an positive ionotropic effect on the heart and increase frequency and the strength of the heart beat
What does the ionotropic effect of catechloamines cause in terms of blood vessels and blood pressure?
The increased frequency and strength of the heartbeat causes vasoconstriction - the narrowing of the blood vessels increases heart rate
Why do you go pale when catechloamines have their effect?
Because they shut down the blood vessels of the skin and redirect the blood to the major vessels
Catechloamines target B-adrenoceptors and in the case of the effect on the heart they affect B1 adrenoceptors. Using this, how would you treat someone with hypertension?
Hypertension = high blood pressure so you want to inhibit the effect of the catechloamines on the heart so you would therefore use a B1 adrenoceptor selective antagonist such as atenolol
What is hypotension?
Low blood pressure
What is hypotension caused by?
Failure of the adrenal medulla (rare)
What can hypotension be treated with?
Agonists of B-adrenoceptors
What could be a reason for having hypertension that involves the adrenal medulla?
Tumours like neuroblastoma of the adrenal medulla cause secretion of the catecholamines and therefore hypertension - removed by surgery
What are the hormones of the adrenal cortex collectively known?
Adrenocortical hormones
What kind of hormones are the adrenocortical hormones and what structure are they based on
They are steroids based on the structure of chlolesterol
What are the two major classes of adrenalcortical hormones?
- Adrenocorticosteriods
2. Sex Hormones
What can adrenocorticosteroids be broken down into?
- Mineralocorticoids
2. Glucocorticoids
What is an example of a mineralocorticoid?
Aldosterone
What is an example of a glucocorticoid?
Cortisols (e.g. hydrocortisone and corticosterone)
What are two examples of sex hormones?
Androgens (male sex hormones) and oestreogens (female sex hormoles)
What are the two major classes of adrenocortical hormones?
- Mineralocorticoids and Glucocorticoids
2. Sex Hormones
What kind of receptors do these adrenocortical hormones act on?
Nuclear receptors
The action of adrenocortical hormones is that it leads to protein production. How does it do this?
- hormone binds nuclear receptor
- hormone-receptor complex under goes a conformational change and attaches to hormone response elements on the DNA
- recruits RNA polymerase to make mRNA
- protein synthesis
What are hormone response elements?
Sequences on the DNA that the receptor binds to
Is action of the adrenocortical hormones fast or slow compared to the catechloamines?
Slow as protein synthesis can take hours/days
What property of the adrenocortical hormones means they can reach the nuclear receptors?
They are lipophillic/hydrophillic so can pass through the cell membrane by passive diffusion
What are some other examples of lipophillic ligands for nuclear receptors?
Vitamins A and D derivatives
Describe the sequence of events that occurs after the glucocorticoid cortisol is released into the blood stream by the adrenal gland?
- Enters the cell via passive diffusion
- Finds a nuclear receptor in the cytoplasm of nucleoplasm
- Binds and induces a conformation change in the receptor
- Receptor reveals a nuclear target signal
- Receptor binds to the hormone response elements on the DNA
- Regulates gene expression and therefore protein synthesis
Where are nuclear receptors found and what makes them able to be in this enviroment?
In the cytoplasm of the nucleoplasm and they are soluble proteins so mix well with aqueous enviroments
Describe what an oestrogen receptor agonist would do and what it would be used for?
Minic the action of oestrogen on nuclear receptors and used for Hormone replacement therapy in post menopausal women
Given an example of a oestrogen receptor agonist
Conjugated equine estrogens
Given an example of what a glucocorticoid receptor agonist would do and be used to treat?
Would minic the action of cortisols such as hydrocortisone and so could be used treat inflammation
Given an example of a glucocorticoid receptor agonst?
Hydrocortisone or dexamethasone
What would a mineralocorticoid receptor antagonist do and when could this be used?
It would block the ability of the mineralocorticoid to increase water volume which would reduce inflammation in patients with oedema
Give an example of a mineralocorticoid receptor antagonist
In order to decrease water volume lots of urine is produced so a diuretic such as spironolactone
What would an oestrogen receptor antagonist do and what would it be used to treat?
Would block the action of oestrogen for prevention and treatment of breast cancer
Given an example of an oestrogen recptor antagonist?
Tamoxifen
What would an androgen receptor antagonist do and when would it be used?
Block the action of male sex hormones such as testotersone and used in the treatment of prostate cancer
What is an example of an androgen receptor antagonist?
Bicalutamide/casodex
What is an example of a mineralocorticoid?
Aldesterone
What is the function of mineralocorticoids?
They maintain the salt balance in the body
How do mineralocorticoids maintain the salt balance?
They exchange potassium for sodium and water
How do mineralocorticoids regulate blood volume?
Water always follows sodium so by regulating the salt levels they also regulate the water metabolism
How do mineralocorticoids increase blood pressure?
By increasing the water volume they increase the blood volume and therefore increase blood pressure
How is mineralocorticoid production regulated?
Through the Renin/Angiotensin system
How is low plasma sodium detected?
By the kidneys
After detection of the low plasma sodium an enzyme is produced; what enzyme is this and what does it convert?
Renin and converts angiotensinogen to angiotensin 1
What is angiotensin 1 converted to and what converts it?
Converted to angiotensin 2 by the angiotension converting enzyme (ACE)
What does angiotensin 2 act on?
G protein coupled receptors on the adrenal cortex
What does angiotensin 2 cause the production of by the adrenal cortex?
Mineralocorticoids (mainly aldosterone)
How does aldosterone then increase plasma sodium?
By acting on the distal renal tubules which causes Na+ reabsorption and increased secretion of K+
What receptors does aldoesterone act on?
Nuclear receptors of the kidney ONLY
What receptors does aldosterone act on?
Nuclear receptors of the kidney ONLY
Name an antagonist for aldoesterone at these receptors, what kind of antagonist is this?
Spironolactone which is a reversible competitve antagonist - means Na+ is not reabsorped so can be used to treat high blood pressure
Since aldosterone is an example of a hormone that acts on nuclear receptors how does this end up with the increased absorption on sodium?
The hormone-receptor complex interacts with DNA to increase synthesis of proteins that will produce more sodium channels in the membrane of the renal cells containing the nuclear receptors
What are the three main actions of glucocorticoids?
- Glucose metabolism
- Negative feedback on anterior pituitary and hypothalamus
- Anti-inflammatory and immunosupressive effects
What are the two main actions of glucocorticoids?
- Glucose metabolism
3. Anti-inflammatory and immunosupressive effects
Glucose levels need to be elevated in times of stress. What senses this stress?
The hypothalamus
What does the hyporthalamus release?
Corticotrophin releasing factor
What does corticotrophin releasing factor act on and what does this then produce?
The GPCRs of the Anterior Pitutiary which then releasing Corticotrophin
What does corticotrophin then act on and what does this produce?
The adrenal cortex which then produces the glucocorticoids
How do glucocorticoids affect metabolism?
by elevating blood glucose levels by causing increased breakdown of fats and proteins to glucose as well as decreasing the uptake of glucose by carbohydrates
How do glucocorticoids have anti-inflammatory properties?
They block the leaking of lymphocytes from blood vessels to the site of infection
How do glucocorticoids have immunosupressive properties?
they inhibit the production an immune mediator which ultimately leads to supressed T cell and B cells
Which enzyme do glucocorticoids inhibit in order to have their properties?
Phospholipase A2
What does phospholipase A2 do?
Involved in the production of arachidonic acid, prostaglandins and leukotrienes
Name a glucocorticoid agonist that could be used to treat asthma? How is it applied?
Beclamethasone is inhaled
Name a glucocorticoid agonst that could be used to treat skin inflammation. How is it applied?
Bethamethasone is applied topically
Name 6 treatments for which glucocorticoid agonsts could be used.
- Asthma
2. Autoimmune diseases
Name 6 treatments for which glucocorticoid agonsts could be used.
- Asthma
- Autoimmune diseases
- Cancer Therapy
- inflammatory Diseases
- Allergic Responses
- Organ Transplant
