Adrenal Physiology Flashcards
Adrenal gland location
Cortex derived from…
Cortex zones (hint:GFR)
Cortex secretions (hint: salt, sugar, sex)
Medulla derived from…
Medulla secretions (hint: mine cats)
Location: above kidney (aka suprarenal gland)
Adrenal cortex- zona glomerulosa, zona fasciculata, zona reticularis (GFR);
derived from mesoderm, makes up 90% of the adrenal gland
G- secretes mineralocorticoids (salt)
F- secretion of glucocoriticoids (sugar)
R- secretion of sex steroids
Adrenal medulla- secretion of catecholamines, derived from neural crest cells
Blood flows from where to where in the adrenal gland?
What’s cortisol’s “permissive effect” on catecholamines?
Blood flows from cortex into the medulla
Cortisol has a permissive effect on the catecholamines: cortisol can flow down into the medulla and influence catecholamine synthesis
Process of steroidogenesis:
What’s the precursor molecule formed from cholesterol
How’s it formed and what’s the enzyme that does this (hint: SCC by CYP)
Which hormones can result from this precursor?
What’s the weak steroid that forms?
How do you form testosterone and estradiol from this pathway?
Pregnenolone: becomes aldosterone; cortisol; androstenedione from which estradiol is made via the aromatase reaction, and testosterone (can also become estradiol via aromatization) comes from 17 BHSD
DHEA is another precursor of androstenedione, and it’s a weak steroid
Role of SF1 in steroidogenesis (promotes synthesis and uptake of cholesterol. Which proteins does SF1 stimulate that do this?)
SF1 defect causes…?
SF1 important factor for adrenal synthesis: stimulates steroidogenesis by stimulating HMG coA synthase (cholesterol synthesis) and the STAR protein (cholesterol uptake)
SF1 defect - adrenal hypoplasia (adrenal insufficiency)
Things that promote HPA axis
Difference between primary and 2ndary adrenal insufficiency?
Things that promote it: Stress (physical/emotional), hypoglycemia, cold and pain
Primary adrenal insufficiency: adrenal gland itself has a problem (mineralocorticoid defect, high K+, salt craving)
Secondary adrenal insufficiency: hypothalamic or pituitary problem but gland itself is fine; no mineralocorticoid defect
Briefly describe te ACTH signaling cascade (which 2 things happen when ACTH binds its receptor; both involve cAMP)
Why is hormone synthesis zone speficic?
ACTH binds to cell surface receptors, activating adenylyl cyclase, increasing cAMP. Activation of StAR. Also, causes upregulation of cholesterol receptors in adrenal surface; causes increase in free cholesterol formation and lipoprotein uptake by the adrenal cortex;
Cholesterol taken up by STAR protein into mitochondrial membrane by STAR; initiates steroidogenesis
Different zones have different enzymes so they can only synthesize the hormone specific to the zone because of the enzymes
2 pathways of steroid hormone receptors
What happens when cortisol binds its receptor? (2 effects; give e.g. of each) (how does it enter the cell?)
Mostly acts through intracellular receptors that then go to the nucleus and initiate gene transcription;
cell surface receptor pathway is the minor pathway that involves rapid response
Cortisol diffuses thru the membrane and will have either a positive or negative influence
Positive = upregulating gene transcription
Negative: steroids tend to dampen the immune system (for example)
Physiological effects of cortisol revolve around mainly: generating a bunch of energy
making people obese
making catecholamines
causing osteoporosis
How does each of the above happen?
Does all this happen at normal or excess cortisol levels?
Increasing gluconeogenesis/decreasing glucose utilization/promotes muscle protein catabolism; side effect = hyperglycemia/diabetes
Breaks down fats and redistributes it (obesity due to cortisol tends to be centripetal)
Decreases bone formation and collagen synth by decreasing Ca absorption; increases bone resorption (increases serum ca) (too much steroid can cause osteoporosis)
Cortisol also increases norepinephrine to epinephrine conversion
Happens at excess cortisol levels; normal levels = maintenance of homeostasis
Hemodynamic effects of cortisol
(hint: amine press; VascFluid; anti-ADH; MR effect)
Increased response to catecholamine pressor effect
Antagonizes ADH
Maintains vascular integrity and fluid volume
Mineralocorticoid effect
Immune effects of cortisol
(anti-inf by CLP, leuk, doesn’t mediate)
Anti-inflammatory by regulating (cytokines, leukotrienes and prostaglandins)
Decreases leukocyte (basophil and eosinophils), and lymphocyte activity
Impairs cell mediated immunity
CNS effects of cortisol
(hint: controls the “feels” and gives you the munchies)
Modulates perception and emotion
Increases appetite
Secondary activation of cortisol via __
(Cortisol excess feeds back on this)
Vasopressin
Metabolism of Cortisol (converted to what via 11BHSD2?)
Role of 11BHSD1
What’s the MR effect of cortisol?
Inhibition of 11BHSD2 by __ (the real European, black kind)
Where is this happening?
Cortisol converted to cortisone via 11-B-HSD2
11BHSD1 converts cortisone to cortisol
Cortisol can bind to MR and augment mineralocorticoid effects
Licorice can bind and block 11BHSD2; pts get syndrome of apparent mineralocorticoid excess (more cortisol-mediated MR effects), symptoms of hyperaldosteronism
All this happens mostly in the kidney
Downstream effects of excess cortisol
(explain the pathway below)
Increased gluconeogenesis = increased insulin =
Decreased GLUT4 translocation to the membrane = insulin resistance = hyperglycemia
Increased lipolysis = increased glucose
Brain – CNS modulates emotion
Skin – thinning and bruising
GC effects on immune system (which cells are affected?)
Effects on IL 1 and 2 release from which cells?
Effects on cell survival
Effects on T helper and T suppresor cells and B cell action
Effect on prostaglandins and leukotrienes
Blocks Macrophage release of IL 1, which would normally activate T cells; blocks T cell release of IL 2, which would normally activate T helper and T suppressor cells that activate B cells to release antibodies
Also causes T cell death
Inhibits prostaglandin mediated vasodilation, leukocyte attraction, increase capillary permeability
Inhibits leukotriene mediated phagocytosis
RAAS (briefly review the system)
Catecholamine actions:
Alpha 1 pathway (cAMP or PLC); effects
Alpha 2 pathway
Beta pathway
Alpha 1 agonists used for people w/ hypotension or who are in shock (has vasoconstrictor effects); pathway is PLC – IP3 pathway
Alpha 2 agonists: pathway is AC – cAMP, also promotes vasoconstriction
Beta agonist pathway: also cAMP; cardiac muscle contraction but vasodilation (smooth ms relaxation, important for asthma coz you can expand bronchioles)
Metabolism of catecholamines
Free catecholamines >> free metanephrines >> sulfate conjugated metanephrines
Classical vs non classical CAH (which enzyme is defective, when does disease manifest, patial or complete defect)
Symptoms mimic __ in women
Effect of the enzyme defect (which direction does cortisol synthesis pathway now go?)
Most common = 21 hydroxylase defect (classic)
Later on in life – symptoms mimic PCOS; non classic = partial defect of 21 hydroxylase
Cortisol production decreased and pathway driven more towards androgen production
