Lecture 38: The HPA Axis Flashcards
Why do we care about the HPA axis?
Because it functions to regulate stress
What is the HPA axis?
The hypothalamic pituitary adrenal axis
In the HPA, what are the key hormones?
- Corticoid releasing factor (CRF) from hypothalamus
- Adrenocroticotrophic hormone (ACTH) from anterior pituitary
- Glucocorticoids and catecholamines from adrenal gland
What are the function of glucocorticoids and catecholamines?
- metabolic mobilization
- increased HR, blood pressure and respiration
- redistribution of blood flow
- suppression of immune/digestive systems
What happens to immune and digestive system during stress?
Suppression
What is the primary glucocorticoid in humans?
Cortisol
-can bind to both minearalocorticoid and glucocorticoid receptors
What is the primary mineralocorticoid in humans?
Aldosterone
What are examples of synthetic agonists?
- Dexamathasone (GR)
- Prednisone (GR)
- Spironolactone (MR)
How does cortisol mediate stress response?
By binding to BOTH Mineralocoriticoid receptor and GR
What happens when cortisol binds to GR?
Increased gene expression to mediate long term effects of stress (slow-acting)
Fast acting mechanisms still being researched
What is the marker for HPA dysfunction in mental disorders?
Cortisol concentration in blood
- In patients with depression, high cortisol
- however, cortisol level is NOT diagnostic…because it is all about comparison to baseline
What is the significance of diurnal rhythm in the body? Significance?
From 4-10am, Glucocorticoid RELEASE is at its greatest
When treated with prednisone, there is SUPPRESSIVE effect on cortisol because there is a negative feedback mechanism that prevents the GC spike in the morning
When is glucocorticoid (cortisol) release the greatest?
4-10am
What are the consequences of treating patients with prednisone?
Mental disorders such as
- Depression
- panic
- hypomania/mania
- Delirium
What are the acute effects of glucocorticoid?
- promoting survival
- alter metabolism
- maintain fluid balance
- affects multiple brain regions (increase emotional/habitual memory while diminishing declarative/episodic memory/cognition)
- Inhibit nonessential systems
- immune cells, inflammatory reactions, pituitary gonadotropins, inhibits osteoblastic activity
- Decrease bone mass
What is the CNS response to chronic corticosteroids (stress)?
-promotes emotional (amygdala) and habitual (striatum memory Diminishes declarative (hippocampal) memory
What are the pathological results of cortisol release?
- Sleep disturbance
- Attentional disruption
- Hippocampal memory IMPAIRMENT (episodic memory)
- Amygdala memory enhancement (PTSD
- CV disease
- HTN, clotting, fat deposition
- Sexual disorders
- Susceptibility to infection
What is the takehome point of HPA stress regulation?
Acute stress is adaptive
Chronic stress leads to pathology
What is the relationship between addictive behaviors and HPA activity?
Addictive behavior DECREASES HPA activity and thus stress
- consumption of high fat foods/drugs = termination of HPA response to stress
- decreased amygdala
- cannabinoid, opioid and GABA inhibit acitivyt of brain regions that drive HPA activity
- Withdrawal of drugs of abuse or high fat foods are HPA activating and perceived as stressful
What is the effect that cortisol has on the brain?
- Hippocampal neurons DECREASE in arborization
2. Amygdala neurons INCREASE in arborization
What is the difference between cortisol levels in depressed patients and PTSD patients?
Depression = HIGHER cortisol (as expected)
PTSD patients = LOWER cortisol (unexpected)
When you give someone with PTSD glucocorticoid, what happens?
Brain HYPERSUPPRESSES cortisol release
Unknown if it is the TRAUMA or the DISORDER that leads to lower cortisol levels
What is the significance of Corticotrophin Releasing Factor (CRF)?
Implicated in the negative effects of stress on psychological health
-secretes ACTH
-initiates SNS
-released ACROSS the brain
CRF receptors EVERYWHERE, like pancreas, skeletal muscle, etc.
Where is CRF produced/released?
Paraventricular nucleus of the hypothalamus
