5. Glucocorticoids and the stress response Flashcards
What is the stress response?
a suite of physiological and behavioral responses to a stressor that help to restore homeostasis
What are the 2 steps of the physiological stress response?
- Sympathetic nervous system
- Quick response system, within seconds
- Release of epinephrine (adrenaline) - HPA Axis (hypothalamic-pituitary-adrenal axis)
– Slower response system, minutes to hours
– Release of cortisol
What hormones are released from the adrenal cortex?
Glucocorticoids e.g. cortisol
Mineralocorticoids e.g. aldosterone
Sex hormones e.g. testosterone
What hormones are released from the adrenal medulla?
Epinephrine
Norepinephrine
Physiological consequences of the stress response: HR O2 Glucose Muscle blood Alertness GIT Immune Eyes
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
Consequences of the stress response, beneficial?
In general, stress is beneficial in the short-term or at mild levels, but can cause major long-term problems if stress is chronic
Chronic stress is associated with which health problems?
– Heart disease – Diabetes – Ulcers – Growth problems – Compromised immune system
Link between cortisol and depression?
• Cortisol elevated in~ 50% of depressed patients
But rhythm in cortisol production (high in morning, 7-9am, low 11pm-4am)
What is the action and purpose of Dexamethasone Suppression Test?
People usually have high cortisol in the morning
• If given Dex —> HPA negative feedback turns this off, so no cortisol surge
Note: Not true of depressed patients
In pit tumour present, DEX has no effect
Depression is a symptoms of…
Cushing’s disease (in high cortisol levels)
Addison’s disease (in low cortisol)
NASA Study;
- To study the relation between elevated stress hormones and the reactivation of Epstein-Barr Virus (EBV) in astronauts.
- To study the effects of stress due to space flight on levels of neuroendocrine hormones and immune cells.
Method?
Results?
Method: • Blood samples were taken for conc of anti-vital antigens/antibodies and stress hormones: 1. Ten days before launch 2. Landing day 3. Three days after landing • Urine samples for detecting hormones.
Results:
• There was significant rise (8- to 64-fold increase) in the levels of EBV antigens in blood samples taken before, during and after the flight. (chronic stress, may have triggered the replication)
• The levels of anti-EBV antibodies continued to decrease from before to after flight.
• 11 astronauts showed evidence of EBV reactivation, and each showed increases in urinary epinephrine and norepineprine (stress hormones).
Conclusions of NASA study?
- There wasadecreaseinthevirusspecific antibodies in all the astronauts.
- Reactivation of EBV occurred in 11/28 astronauts.
- Urinary cortisol and catecholamines were elevated after flight.
- Stresses due to space flight lead to decreased virus specific T-cell immunity and reactivation of EBV.
What is the classical mode of glucocorticoid action? i.e. transactivation
Glucocorticoid
- -> GRE activation and trascription of anti-inflammatory gene
- -> Direct production of anti-inflammatory protein (so dampens down ability to make immune response)
What is the transrepression mode of glucocorticoid action?
Glucocorticoid and cytokine entry to cell
- -> TF binding site stimulated by cytokine upstream of inflammatory gene.
- -> Glucocorticoid INHIBITS transcription
- -> Inflammatory protein not produced
Name 3 main synthetic glucocorticoids used?
Predniose
Prednisolone
**Dexamethasone ** Due to high potency, few days of activity
