HPA Axis Flashcards
Is the response to stress all about the hypothalamus?
Nope. Higher cortical areas are involved in determining that the individual is somehow threatened and should be stressed.
Two main systems for responding to stress? Which is fast, which is slow?
Sympathetic nervous system - fast
HPA axis - slow
MCAT review: What’s the basic pathway from hypothalamus to cortisol?
Hypothal makes CRF –> CRF stimulates ant. pituitary to make ACTH –> ACTH stim adrenal medulla to make glucocorticoids.
For a single point-like bolus of stress, when does the cortisol response peak?
At 30 minutes.
What’s one way that glucocorticoid negative feedback occurs?
Inhibition of of CRF release from the hypothalamus.
Review: What’s the primary glucocorticoid?
Cortisol
To what receptors does cortisol bind?
GR (glucocorticoid receptor) and MR (mineralocorticoid receptor).
Note that cortisol actually binds MR better than does aldosterone.
How can cortisol be prevented from binding to MR?
It can be converted to cortisone by 11-beta-hydroxysteroid dehydrogenases
What are 2 synthetic GR agonists?
1 synthetic MR agonists?
GR: dexamethasone and prednisone
MR: Spironolactone
Does cortisol normally cross the placenta?
No, it is usually converted to cortisone, but this can be overwhelmed when there’s a lot of maternal stress.
What has higher affinity for glucocorticoids, MR or GR? How does this relate to their roles?
MR - high affinity, for maintaining “basal HPA tone”
GR - low affinity, responsible for neg. feedback
Review: What kind of receptor is GR? Give a brief description of how it works.
Cytosolic receptor is sequested (by HSPs) in the cytosol until it is bound by ligand. When the ligand binds, GR translocates to the nucleus and acts as a transcription factor.
(note that this mechanism inadequately explains how rapidly cortisol acts)
Review: How does cortisol relate to circadian rhythms?
It peaks, on average, at about 7-8am - which is a socially acceptable time to wake up.
How do people’s aldosterone, renin, and cortisone adjust to circadian shifts (i.e. night shift work)?
Adolesterone and renin adjust, but cortisol does not. It keeps peaking at 7-8am.
What effect do exogenous glucocorticoids such as prednisone have on cortisol?
These suppress endogenous glucocorticoid release via negative feedback. (secondary adrenal insufficiency - why you must taper patients off prednisone)
