Adrenal Physiology Flashcards
1) Understand adrenal gland structure 2) Understand regulation and actions of.. - Aldosterone - Cortisol - Androgens - Catecholamines
Review: 3 layers of the cortex from the outside in? What does each do?
GFR–> Medulla
Glomerulosa - Salt (Aldosterone)
Fasciculata - Sugar (Glucocorticoids)
Reticularis - Sex (Androgens)
Medulla- STRESS ( Epinephrine, Norepinephrine)
What class of molecule are the hormones made in the adrenal cortex? What are they all derived from?
Steroid class
- All derived from cholesterol
Do steroids only bind to nuclear receptors?
No, they can also modify enzyme activity by binding surface receptors.
What is the rate limiting step of all steroidogenesis?
Cleavage of cholesterol to pregnenolone by CYP11A1 in the mitochondria.
What steroid hormone synthesis enzyme is located only in the zona glomerulosa?
Aldosterone Synthase (makes aldosterone from corticosterone)
What are 3 things that drive aldosterone release?
1) Increased angiotensin II.
2) Increased serum K+.
3) Increased ACTH. (Lesser stimulus)
2 things that drive cortisol release?
1) ACTH
2) Arginine vasopressin (Lesser stimulus)
What drives androgen release from the adrenal cortex?
ACTH.
Upon what hormone from the adrenal cortex is catecholamine synthesis dependent?
Cortisol
Where are the juxtoglomerular cells? What do they do? (What do they make?)
They surround the afferent arterioles to glomeruli and near the distal tubules in the kidney.
- Can sense changes in blood volume
- Sense perfusion pressure
- Sense [Na+] in distal tubule
They make renin.
2 ways to stimulate renin production?
1) Low volume in the afferent arterioles.
2) Decreased Na+ concentration in the distal tubule.
2 ways to decrease renin?
1) Increased afferent arteriole volume.
2) Increased Na+ concentration in the distal tubule.
What does renin do? What are the downstream effects of this?
Renin converts Angiotensinogen to Angiotensin I.
Angiotensin I is converted to Angiotensin II by ACE.
Angiotensin II stimulates aldosterone release.
Aldosterone increases water and Na+ resorption (and increases K+ secretion).
2 Main effects of aldosterone? How does it do that?
1) Increases blood volume
2) Regulate salt/water homeostasis
- Increases Na+ absorption and K+/H+ excretion.
- It does this by up regulating Na+/K+ channels in the distal cortical collecting duct. (more on this in renal)
3 ways to increase ACTH release?
1) CRH.
2) Arginine vasopressin.
3) Inflammatory cytokines.
What is the receptor for ACTH?
Melanocortin 2 receptor.
What does ACTH binding to its receptor do? (2 things)
1) Increases LDL receptors -> more cholesterol brought into cell.
2) Increases CPY11A1 expression for steroid synthesis.
Review: How is ACTH synthesized, and what else is made with it?
As a long molecule called POMC. Melanocyte stimulating hormones are part of POMC, and released simultaneously with ACTH.
- ACTH has weak affinity for Melanocortin Receptor 1
- When there is huge amount of ACTH–> it can bind to MR1 and result in hyper pigmentation
Cortisol has a lot of effects. What effects does it have on bone and skeletal muscle?
Bone: increases osteoclast activity -> osteoporosis.
Skeletal muscle: Amino acid release, insulin resistance.
Review: To what hormone does the mineralcorticoid receptor have the highest affinity? How does the body accomodate? (Explain the cortisol shunt)
Mineralcorticoid receptor actually has higher affinity for cortisol than it does for aldosterone
(Our body has way more cortisol than aldosterone)
In aldosterone-sensitive tissues, such as the kidney, cortisol is converted to cortisone ( Which is inactive–> lets aldosterone bind)
What enzyme converts cortisol to cortisone?
11-beta HSD2. (hydroxysteroid dehydrogenase)
…it’s been mentioned a few times.
What pharmacological activity does licorice have? What does an overdose cause?
It inhibits 11-beta HSD2 (Inactivates Cortisol Shunt–> thus more cortisol, less cortisone)
Overdose mimics hyperaldosteronism -> HYPERtension and HYPOkalemia.
What happens to androstenedione in peripheral tissues?
It gets converted to testosterone and estrone.
Review: What tells the adrenal medulla to release catecholamines?
Sympathetic nervous system activation
B&B Review: What starting product are catecholamines made from? What is the rate limiting step and what enzyme does it? What enzyme converts NE to Epi?
NE and Epi (and dopamine) are made from tyrosine.
RLS: Tyrosine –> Dopa by Tyrosine Hydroxylase.
NE–> Epinephrine by PNMT
What specific effects does cortisol have on chromaffin cells?
Cortisol causes upregulation of PNMT, such that the adrenal medulla secretes more Epi (80%) than NE.
What are catecholamines converted to in the blood?
Metanephrines… which have also have a short half life. These are all then converted to VMA.
(this is probs pretty low yield)
What’s the main point about the different adrenergic receptors, for this lecture?
What do alpha1 and beta2 receptors do?
They’re in different places, and have different activities.
Alpha1 causes peripheral vasoconstriction -> increased BP.
Beta2 causes vasodilation in vessels supplying heart and skeletal muscle, and bronchodilation.
ALL act on the different elements of the Fight or Flight Response
What is the main site of androgen production in women? What is it in men?
In women: adrenal glands (ovaries make minor component)
In men: testes (adrenal glands minor component)
