SM150 Adrenal Medulla

Question 1

Ontogeny of chromaffin cells?

Answer 1

Neural crest –> SA progenitor (in the presence of GC) –> chromaffin cell –> epinephrine or norepinephrine cell

SA progenitor (in the presence of FGF and NGF) can also turn into a sympathetic neuron that releases NE, ACh, or NO

Question 2

Catecholamine synthesis? Rate limiting step? Compartments where reactions happen?

Answer 2

Tyrosine –> Dopa –> Dopamine –> Norepinephrine –> Epinephrine.

Tyrosine hydroxylase (first reaction) is rate-limiting.

Tyr comes in from outside the cell. Converted to DOPA and then DA in cytoplasm, taken into granule and converted to NE, released back into cytoplasm and converted to Epi, then back into granule.

Question 3

Are chromatin cells ever sensitive to circulating factors? What can change whether or not they are sensitive?

Answer 3

Early on before innervation. Can revert with phenochromocytoma.

Question 4

Enzymes that metabolize NE and Epi?

Answer 4

COMT and MAO. Both pathways produce VMA as a final metabolite.

Question 5

How do catecholamines influence adrenal steroid secretion?

Answer 5

Signals from sympathetic/adrenergic nerves alter adrenal response to ACTH.

Sympathetic activity is also responsible for compensatory adrenal hyperplasia following adrenalectomy.

Question 6

Epi vs. NE potency: alpha1, alpha2, beta1, beta2?

Answer 6

a1: Epi > NE (smooth muscle contraction)
a2: Epi > NE (vasoconstriction)
b1: Epi = NE (heart rate)
b2: Epi&raquo_space; NE (smooth muscle relaxation)

Question 7

What are the effects of catecholamines on glucose metabolism? Fat metabolism? Protein metabolism? Energy metabolism? Water and electrolyte metabolism?

Answer 7

(increases everything except protein degradation)

Mobilizes glucose and lipid stores to make more energy available. Slows protein degradation by inhibiting ubiquination. Increases energy expenditure in brown fat and other peripheral tissues. Increases Na reabsorption and K entry into cells.

Question 8

Epi vs. NE: CV effects

Answer 8

Epi: increase systolic BP, decrease diastolic BP (dilation of the vascular bed). Pulse pressure increases, MAP goes up, HR goes up (adrenergic)

Norepi: increase systolic and diastolic BP. No change in pulse pressure, MAP goes up, HR goes down (vagal)

Question 9

Conditions associated with increased medullary secretion?

Answer 9

Exercise, stress (psychological or physiological), starvation/fasting

Question 10

Vasovagal syncope changes in medullary/SNS secretions?

Answer 10

Sympathetic nerve deficiency (less NE released from cardiac sympathetics and less efferent signals to skeletal muscle) + increased release of circulating epi (compensatory)

Question 11

Do men or women have more epinephrine? Is weight loss greater in men or women?

Answer 11

Both men.

Question 12

Is epinephrine higher or lower in obesity? Metabolic syndrome?

Answer 12

Both have lower epi. Most obesity Rx’s stimulate epinephrine (physical activity, calorie restriction, available drugs, eating peppers).