Glucocorticoids and the stress response Flashcards
What is a Stressor?
Stressor is a stimulus that disrupts homeostasis and causes the stress response
- Examples: A predator is running towards you, a difficult and important exam, imagined events
What is a Stress response?
Stress response is a suite of physiological and behavioural responses to a stressor that help to restore homeostasis
Explain what is happening in the Stress response?
Stress Response / Fight or Flight response;
- 2 step physiological stress response
1). Sympathetic nervous system (fast/short-term response)
- Quick response system within seconds
- Release of Epinephrine (adrenaline)
2). HPA Axis (Hypothalamic-pituitary-adrenal axis);
- Slower response system, minutes to hours (long-term)
- Release of cortisol
What does the Adrenal Cortex and Adrenal Medulla release?
Adrenal Cortex;
- Glucocorticoids (e.g cortisol)
- Mineralocorticoids (e.g aldosterone)
- Sex hormones (e.g testosterone)
Adrenal Medulla;
- Adrenaline/epinephrine
- Noradrenaline/Norepinephrine
What makes up the HPA Axis?
Hypothalamus (brain) release CRH (corticotrophin-releasing hormone) which stimulates the Pituitary Gland (brain) to release ACTH (adrenocorticotrophic hormone) which stimulates the Adrenal cortex (on top of kidney) to release Cortisol.
Cortisol has a negative feedback system to turn off CRH production by hypothalamus
What are the consequences of the Stress Response on the body ?
Immediate effects;
- Increased heart rate
- Increased oxygen intake
- Increased blood glucose levels
- Increased blood flow to muscles
- Increased alertness
- Inhibition of digestion, immune system
- Release of endorphins
- Dilation of pupils
Is the Stress response a good or bad thing?
Short term vs Long term consequences
- In general stress is a beneficial in the short-term or at mild levels but can cause major long-term problems if stress is chronic
What problems can Chronic Stress be linked to ?
Chronic Stress be linked to;
- Heart disease
- Diabetes
- Ulcers
- Growth problems
- Compromised immune system
What is the link between cortisol levels and depressed people, and cortisol release routine?
Cortisol is elevated in around 50% of depressed patients
But rhythm in cortisol production is high in the morning (7-9am) and low (11pm-4am)
- Relation to sleep disturbance in depression ?
The Dexamethasone Suppression Test shows;
- People usually have high cortisol in morning
- If given Dexamethasone, HPA negative feedback turns off, so no cortisol surge
- Not true of depressed patients
So the test just tells us if you have abnormal production of cortisol throughout day
So what is the link between Cortisol and Mood then ?
Cortisol and Mood;
- Depression is a symptom of Cushing’s disease (increased ACTH & high cortisol)
- But also typical of Addison’s disease (low cortisol, adrenal insufficiency)
- Cortisol is Biphasic as both these patients susceptible to depression - low and high cortisol, so whether cortisol is low or high will get depression, want cortisol levels in middle.
How does the Stress response system affect the immune system ?
Stress response system affect the immune system;
- 1st few minutes - immune system is enhanced
- After about an hour of stress - immune system returns to normal
- Chronic stress surpasses immune system functioning
(Can use clinically if someone has an overactive immune system can mimic stress with synthetic glucocorticoid and bring immune back to normal!)
How does Cortisol affect stress?
Cortisol is a key anti-stress hormone;
- Cortisol helps reduce inflammation during stress, but also acts as an immunosuppressant.
- Various components of the immune system may be influenced due to cortisol
A study was carried out at a University in Korea where they measured students bloods on the day of an exam and four weeks later, what were the significant changes?
They found the students had Lowered levels of Interferon gamma (IFN-y) due to stress, which is normally released by T-lymphocytes and natural killer (NK) cells
They also has lowered T-helper 1 (TH1) cellular immunity
Conclusions;
- Cytokine profiles were take which served as an indirect link to the immune system
- There was a significant decrease in the number of macrophages, interferons, lymphocytes and natural killer (NK) cells.
What did the Space flight study show?
Astronauts bloods were taken before, during and after take off as they would experience the following stresses;
Physical;
- G-force acceleration
- Cosmic radiation
- Pressure variations
Emotional stresses;
- Flight tasks
- Public events
- Being strapped to a rocket
The study looked at the amounts of stress hormones and reactivation of Epstein-Barr Virus (EBV). 80 - 90% population are positive for EBV antibodies but quiescent, unless very immunocompromised as stress reactivates the virus.
The study showed that;
- Reactivation of EBV occurred in 11/28 of the astronauts
- Urinary cortisol and catecholamines were elevated after flight
- Stressed due to space flight lead to decreased vis specific T-cell immunity and reactivation of EBV.
How do Glucocoticoids work in a cell?
Glucocorticoid crosses into the cytosol which crosses and interacts with glucocorticoid receptor which then interacts with a response element (GRE = glucocorticoid response element) which then drives upwards the production of an anti-inflammatory gene, making a anti-inflammatory protein therefore dampening down the immune responses
How do cytokines affect the function of Glucocoticoids in a cell?
Proinflammatory cytokines drives forward the production of something which causes inflammation.
Cytokine binds onto its response element and drives and inflammatory gene and produces and inflammatory protein
Addition of glucocorticoid is blocking the production of the inflammatory protein, so it will not be made at the same levels
What are the features of Synthetic Glucocorticoids ?
We can use Synthetic Glucocorticoids to dampen down patients who’s bodies are making inappropriate autoimmune responses like rheumatoid arthritis, IBS, etc
Treat with synthetic steroids
Can tailor immunosuppression to condition you are treating
Examples;
- Hydrocortisone - Potency 1 (same as cortisol), t1/2 8 hours
- Prednisolone (most prescribed) - Potency 4, t1/2 16-36 hours (mild steroid)
- Dexamethasone - Potency 25-80 (Super potent!), t1/2 36-54 hours (very strong steroid)
