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HORMONES OF THE

ADRENAL MEDULLA

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The adrenal medulla is an extension of the

sympathetic nervous system

While not necessary to life, they are

required for stress adaptation

Products are the catecholamines

(dopamine, epinephrine, norepinephrine)

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SYNTHESIS OF CATECHOLAMINES

1. Ring hydroxylation

Tetrahydropteridine iscofactor

Rate-limiting step in

catecholamine biosynthesis Competitive inhibition by -

methyltyrosine removal of

cofactor

phenylethanolamine-N

-methyltransferase

1

2

3

4

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SYNTHESIS OF CATECHOLAMINES

2. Decarboxylation

Needs pyridoxal phosphate Alpha-methyldopa is

competitive inhibitor (used in

the treatment ofhypertension)

phenylethanolamine-N

-methyltransferase

1

2

3

4

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SYNTHESIS OF CATECHOLAMINES

3. Side chain hydroxylation by a

mixed function oxidase Ascorbic acid is electron

donor Copper is at the active site

while fumarate acts as amodulator

4. N-methylation

PNMT is induced byglucocorticoids (e.g. duringstress response

phenylethanolamine-N

-methyltransferase

1

2

3

4

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Catecholamines cannot cross the blood-

brain barrier (so L-Dopa is given in

Parkinsons disease) 80% of catecholamines in medulla is

epinephrine

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(500 D)

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CATECHOLAMINE RELEASE

Calcium-dependent

Neural stimulation causes fusion of

storage granules with the plasmamembrane

Stimulated by cholinergic and -

adrenergic agents and inhibited by -adrenergic agents

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CATECHOLAMINE RELEASE

The adrenal medulla, unlike sympathetic

nerves, has no ability to reuptake

discharged catecholamines Half-life: 10-30 secs

Loosely associated with albumin

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Catechol-O-Methyltransferase

Monoamine oxidase

VMA

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dihydropteridine reductase

tyrosine hydroxylase

Dihydroxyphenyl

acetic acid

(VMA)

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MAO inhibitors are used to treat

hypertension and depression

VMA is elevated in patients with tumors ofthe adrenal medulla (Pheochromocytoma)

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CATECHOLAMINE RECEPTORS

1- increase glycogenolysis, smooth musclecontraction

2- smooth muscle relaxation,vasoconstriction

inhibits lipolysis, renin, insulin, platelet

aggregation

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CATECHOLAMINE RECEPTORS

1 increase lipolysis,increase force and rate ofheart contraction

2 increase hepatic gluconeogenesis andglycogenolysis

increase release of insulin and glucagon

relaxes smooth muscles

Beta receptor genes have no introns and arehomologous to rhodopsin (visual responseprotein)

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CATECHOLAMINE RECEPTORS Epinephrine activates alpha and beta receptors

Norepinephrine primarily binds to alpha receptors at

physiologic concentrations

Alpha and beta receptors are G-protein-linked Hormones that bind beta receptors activate adenylate

cyclase, while 2 receptors inhibit adenylate cyclase

1 receptors are coupled to processes that alter

intracellular calcium concentrations or modifyphosphatidylinositide metabolism