1-30 DSA Adrenal Gland DSA Flashcards by Stephen Schaffner

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

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What is 21-hydroxylase? What does its deficiency lead to?

Enzyme in mitochondria of adrenal cortex

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What are the 3 zones of the adrenal cortex?

Zona glomerulosa
Zona fasciculata
Zona reticularis

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What is the main product of the zona glomerulosa? What is the effect?

Mineralocorticoids - 21 carbons

promotes salt and water retentetion

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What is the main product of the zona fasciculata? What is the effect?

Glucocorticoids - 21 carbons

increase blood glucose

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What is the main product of the zona reticularis? What is the effect?

Androgens - 19 carbons

testosterone synthesis in testes
estrogen synthesis in ovaries

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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

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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.

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What tissues is the adrenal gland derived from?

Neuronal (medulla)

Epithelial (cortex)

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What is the origin/composition of the medulla?

Composed of neural crest-derived chromaffin cells

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What is a general effect of cortisol?

– Cortisol suppresses formation of neurons and promotes production of epinephrine

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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

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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

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How is epi and norepi stored?

Stored in chromagraffin granules

complexed with ATP, Ca++, chromogranins

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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

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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

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What do epi and norepi act on?

Act via GPCRs on adrenergic receptors

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What are adrenergic receptors classified by?

Potency of endogenous and pharmacologic agonists and antagonists

Downstream signaling pathways

Location and density of receptors

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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.

1. Increases gluconeogenesis, protein catabolism, lipolysis, and decreases glucose utilization and insulin sensitivity 2. Anti-inflammatory effects •Inhibits phospholipase A2 •Inhibits histamine and serotonin release 3. Suppresses immune responses •T cell suppression (IL-2) •Lyses eosinophils 4. Maintain vascular responsiveness to catecholamines •Maintains normal blood pressure •↓ cortisol → hypotension 5. Inhibition of bone formation •Decreases type I collagen •Decreases osteoblast activity •Decreases gut Ca2+ absorption 6. Increases glomerular filtration rate (GFR) •Causes vasodilation of afferent arterioles 7. 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