1-30 DSA Adrenal Gland DSA Flashcards
What is 17α-hydroxylase? What does deficiency lead to?
Enzyme in mitochondria of adrenal cortex
Helps convert:
pregnenalone into progesterone, then into 11-deoxycorticosterone, and then into corticosterone
Deficiency:
absence of androgens
excess mineralocorticoids
What is 21-hydroxylase? What does its deficiency lead to?
Enzyme in mitochondria of adrenal cortex
What are the 3 zones of the adrenal cortex?
Zona glomerulosa
Zona fasciculata
Zona reticularis
What is the main product of the zona glomerulosa? What is the effect?
Mineralocorticoids - 21 carbons
promotes salt and water retentetion
What is the main product of the zona fasciculata? What is the effect?
Glucocorticoids - 21 carbons
increase blood glucose
What is the main product of the zona reticularis? What is the effect?
Androgens - 19 carbons
testosterone synthesis in testes
estrogen synthesis in ovaries
What is significant about the enzymes in each zone?
Each zone has a distinct set of enzymes to produce different hormones- for example the zona glomerulosa lack 17 α-hydroxylase and will only produce mineralocorticoids
Why is it important to know about the enzymes and intermediates in steroidogenesis?
important to know because enzyme deficiencies will result in characteristic phenotypes
Deficiencies can be partial, resulting in attenuated clinical symptoms.
What tissues is the adrenal gland derived from?
Neuronal (medulla)
Epithelial (cortex)
What is the origin/composition of the medulla?
Composed of neural crest-derived chromaffin cells
What is a general effect of cortisol?
– Cortisol suppresses formation of neurons and promotes production of epinephrine
What is the blood flow of the medulla? Why?
Blood flows from cortex to medulla so cells are constantly exposed to high concentrations of cortisol
What is the percentage of each catecholamine secreted into the blood? Where is it secreted from?
Catecholamine-secreted into the blood from the adrenal medulla
80% epi
20% norepi
How is epi and norepi stored?
Stored in chromagraffin granules
complexed with ATP, Ca++, chromogranins
What controls synthesis of epi and norepi?
Under control of the CRH-ACTH-cortisol axis
- ACTH stimulates synthesis of DOPA
- Cortisol increases PNMT- glucocorticoids are necessary for PNMT expression
What triggers release of catecholamine granules?
Catecholamines are stored in granules and release is triggered by CNS control (acetylcholine release)
- AKA sympathetic inn.
Released in response to:
stress, exercise, hypoglycemia, and hemorrhagic hypovolemia
What do epi and norepi act on?
Act via GPCRs on adrenergic receptors
What are adrenergic receptors classified by?
Potency of endogenous and pharmacologic agonists and antagonists
Downstream signaling pathways
Location and density of receptors
What is the primary action and location of alpha 1 receptors?
Increases IP3 and Ca++, DAG
Increases vascular smooth mm contraction
At sym postsynaptic nerve terminals
What is the primary action and location of alpha 2 receptors?
Decreases cAMP
Inhibits norepi release
Inhibits insulin release
sym presynaptic nerve terminals
beta cells on pancreas
What is the primary action and location of beta 1 receptors?
Increases cAMP
increases cardiac output
In heart tissue, all over
What is the primary action and location of beta 2 receptors?
Increases cAMP
Increases hepatic glucose output
decrease contraction of blood vessels, bronchioles, uterus
In liver, sm mm of vasculature, bronchioles, uterus
What is the primary action and location of beta 3 receptors?
Increases cAMP
Increases hepatic glucose output, increases lipolysis
In liver, adipocytes
What degrades catecholamines?
COMT
MAO
What are the actions of aldosterone?
Controls Na+ resorption in the extracellular space
– Increases Na+ resorption, increases K+ and H+ secretion (increases expression of Na-K pump and Na/K/Cl pump)
How is aldosterone different from ADH?
ADH regulates water balance and plasma osmolarity
What kind of receptor does aldosterone work on? Where are these receptors located?
binds the mineralocorticoid receptor (MR)
In: kidney colon salivary glands sweat glands
What special enzyme do kidney cells have that are responsive to aldosterone?
target cells have 11β-HSD2
- converts cortisol to cortisone
- cortisone has low affinity for MR
Actions of mineralocorticoids can be limited to aldosterone since cortisol is inactivated in tissues with MR
How does lack of aldosterone manifest, symptom-wise?
Hyperkalemia
Hypotension
Metabolic acidosis
How does excessive aldosterone manifest?
Hypokalemia
Hypertension
Metabolic alkalosis
What ‘rule’ from renal should you remember when considering aldosterone?
H+ tends to follow K+
Aldosterone promotes voiding of K+ and H+
- promotes retention of Na+, H2O follows
What is the major regulatory pathway for aldosterone? Is it the same for cortisol?
Major: renin angiotensin system
Cortisol is under ACTH regulation
What are the steps of the RAAS system?
Liver - angiotensinogen
Kidney - renin production
ANG II - Causes an increase in intracellular Ca2+ levels and triggers aldosterone synthesis
What induces renin expression?
Decreased blood pressure/lower blood volume
Both ANGII and aldosterone increase BP
- both inhibit renin expression
Besides RAAS, what also regulates aldosterone production? (minor players)
K+
ACTH
How does K+ regulation of aldosterone work?
Increased extracellular potassium triggers aldosterone synthesis
↑ potassium depolarizes cell membrane and results in an influx of Ca2+, triggers aldosterone synthesis
Regulation: Hyperkalemia → aldosterone secretion → K+ excretion
How does ACTH control aldosterone synthesis?
Controls the first step in aldosterone synthesis- conversion of cholesterol to pregnenolone
ACTH induces secretion of cortisol, corticosterone, and DOC all of which have weak mineralocorticoid activity
What happens to people who oversecrete ACTH?
hypertension
What is a summary for the actions of cortisol?
Increases blood glucose levels
Amino acid mobilization from tissues
Gluconeogenesis in the liver
List all 7 actions for cortisol.
- Increases gluconeogenesis, protein catabolism, lipolysis, and decreases glucose utilization and insulin sensitivity
- Anti-inflammatory effects
•Inhibits phospholipase A2
•Inhibits histamine and serotonin release - Suppresses immune responses
•T cell suppression (IL-2)
•Lyses eosinophils - Maintain vascular responsiveness to catecholamines
•Maintains normal blood pressure
•↓ cortisol → hypotension - Inhibition of bone formation
•Decreases type I collagen
•Decreases osteoblast activity
•Decreases gut Ca2+ absorption - Increases glomerular filtration rate (GFR)
•Causes vasodilation of afferent arterioles - Decreases REM sleep (psychosis)
•Also increases wake time
When do cortisol levels peak? Decrease? What is the name for the pattern of release?
Cortisol is released in a diurnal pattern of secretion
- peaks ~8 am (sounds about right)
- drops off after 8 pm, stays low through ‘night’ hours
Released in a diurnal pattern
What is the immediate action of ACTH?
stimulate mobilization of cholesterol and activate cholesterol desmolase
What is the long term action of ACTH?
stimulate cytochrome P-450 transcription
What happens to increased or decreased ACTH levels?
↓ ACTH- adrenal atrophy in the fasciculata and reticularis
↑ ACTH- increase adrenal size
What happens with excess ACTH?
causes hyperpigmentation due to cross-reaction of ACTH with MCR1 on melanocytes or excess production of MSH
What are the actions of androgens in females?
Presence of pubic and axillary hair, libido
What are the actions of androgens in males?
Same as testosterone
Men do not need adrenal androgens as they are synthesized in the testes
