Lecture 15: Adrenal Physiology Flashcards
What is the set-up of adrenal gland structure?
- Capsule
- Zona glomerulosa
- Zona Fasciculata
- Zona Reticularis
- Adrenal medulla
GFR is the mnemonic
Salt, Stress, Sex
Salt, sugar, sex
What do the adrenocortical hormones come from?
Cholesterol
Synthesized by cytochrome P450 enzymes in mitochondria and smooth ER
What is the rate-limiting step in cholesterol to adrenocortical hormones?
Side chain cleavage of cholesterol to pregnenolone by CYP11A1 in the mitochondria
How do adrenalcortical hormones affect their action?
They are lipid soluble so they pass through cell membrane and binds to receptors that enter the nucleus
What is aldosterone released in response to?
- Increased angiotensin II
- Increased potassium
- Increased ACTH (lesser stimulus)
What does aldosterone regulate?
Blood volume
Salt/water homeostasis
Binds to mineralocorticoid receptor
What is the Renin angiotensin system?
Renin is released in response to
i. decreased afferent arteriole volume (low renal perfusion)
ii. decreased distal tubule sodium concentration (tubuloglomerular feedback)
Renin is DECREASED in response to
i. increased arteriole volume (high renal perfusion pressure)
ii. Increased distal tubule sodium concentration (tubuloglomerular feedback)
What does renin do?
Converts angiotensinogen to angiotensin I
Angiotension converting enzyme (ACE) then takes angiotensin I and converts to angiotensin II
Leads to aldosterone release
So renin —- aldosterone
What does aldosterone bind to?
Mineralocorticoid receptor in the DISTAL cortical collecting duct principal cells
-moves to nucleus to stimulate transcription of genes to increase number of Na and K channels
(increase blood sodium and decrease blood potassium)
Promotes K+ and H+ secretion
What is cortisol released in response to?
- Increased ACTH
2. Increased arginine VASOPRESSIN
What does cortisol regulate?
Binds to glucocorticoid receptor Regulates energy balance Cardiovascular Metabolic homeostasis Immune homeostasis GLUCOSE
What regulates cortisol release?
Circadian rhythm
Physical stressors
Stimulates release of CRH
What stimulates ACTH?
CRH
Arginine vasopressin
Inflammation
What action does cortisol have on ACTH and CRH?
Cortisol inhibits both ACTH and CRH
How is ACTH made?
From proopiomelanocortin (POMC) ACTH is a 38 aa section of POMC
How does ACTH function?
ACTH specific receptor is melanocortin 2 receptor on adrenal tissue and functions
i. to increase LDL recpetors to bring in more cholesterol as precursor for steroid hormones ii. activate CYP11A1 enzyme for cholesterol side chain cleavage iii. ACTH can function as MELANOCORTIN, activating the melanocortin 1 receptor expressed on melanocytes
What are cortisol and ACTH levels like?
Cortisol and ACTH are pulsatile throughout the day
Look at cortisol at 7 or 8am (to check if there is too little cortisol)
At midnight, cortisol should be low…so if you get high levels, then the person might have cushing’s
What are the actions of cortisol?
- liver
- gluconeogenesis
- decrease glucose uptake
- skeletal muscle
- release of amino acids
- blocks insulin dependent glucose uptake (insulin resistance)
- Inflammatory and immune cells
- potent immunosuppressant and anti-inflammatory effects
- decrease macrophage, T cell and mast cell
- peripheral adipose tissue
- release of free fatty acids and glycerol
- Heart
- increases BP via vasoconstriction
- increases adrenergic receptor responsiveness
- Increases vasomotor tone
- Increases osteoclast activity and decrease calcium absorption
- Epinephrine synthesis (activates PNMT enzyme)
What is the cortisol cortisone shunt?
In GCR rich tissues like kidney, cortisol is inactived into CORTISONE
Uses 11BHSD2 to inactivate cortisol to cortisone
To convert cortisone back to cortisol, use 11BHSD1 (lung, brain, adipose tissue)
Cortisol has higher affinity for mineralocorticoid receptor
This shunt is so that the cortisol does not hijack the mineralocorticoid receptors in kidney lmao
What is the significance of 11(beta)HSD2?
It is the enzyme that converts cortisol to cortisone
So inhibitors to 11BHSD2 will lead to hyperALDOSTERONISM
Because cortisol is bound to the mineralocorticoid receptors
Why does licorice cause hyperALDOSTERONISM?
Licorice (glycyrrhizic acid) inhibits 11BHSD2 which means that cortisol cant be inactivated into cortisone
This means cortisol binds the shit out of mineralocorticoid
How is glucocorticoids converted to mineralocorticoids?
By aldosterone synthetase present only in glomerulosa
What do androgens regulate?
Binds to androgen receptor
Regulates pubarche
What are the different types of adrenal androgens?
DHEA DHEAS Androstenedione Increase in production with age Main site of androgen production for women and minor site of androgen production for men Andrenarche begins before gonadarche Timulates pubarche
What are androgens released in response to?
- increased ACTH
What is norepinephrine and epinephrine released in response to?
Sympathetic nervouse system
Synthesis is dependent on highlocal concentrations of cortisol
Binds to adrenergic receptors
What is PNMT?
Phenylethanolamine N-methyltransferase
Convers norepi to epi
Cortisol upregulates PNMT to make epinephrine
How are adrenal medullary catecholamines formed?
Tyrosine enters chromaffin cells and converted by tyrosine hydroxylase to dopa (rate limiting)
Cortisol upregulates PNMT
