HORMONES OF THE

ADRENAL MEDULLA
 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)
 SYNTHESIS OF CATECHOLAMINES
1. Ring hydroxylation
1  Tetrahydropteridine is
cofactor
 Rate-limiting step in
2
catecholamine biosynthesis
 Competitive inhibition by α -
3 methyltyrosine removal of
cofactor
phenylethanolamine-N
4 -methyltransferase
 SYNTHESIS OF CATECHOLAMINES
2. Decarboxylation
1  Needs pyridoxal phosphate
 Alpha-methyldopa is
competitive inhibitor (used in
2
the treatment of
hypertension)
3

phenylethanolamine-N
4 -methyltransferase
 SYNTHESIS OF CATECHOLAMINES
3. Side chain hydroxylation by a
1
mixed function oxidase
 Ascorbic acid is electron
donor
2  Copper is at the active site
while fumarate acts as a
modulator
3 4. N-methylation
 PNMT is induced by
glucocorticoids (e.g. during
4
phenylethanolamine-N
-methyltransferase stress response
 Catecholamines cannot cross the blood-
brain barrier (so L-Dopa is given in
Parkinson’s disease)
 80% of catecholamines in medulla is
epinephrine
(500 D)
CATECHOLAMINE RELEASE
 Calcium-dependent
 Neural stimulation causes fusion of
storage granules with the plasma
membrane
 Stimulated by cholinergic and β -
adrenergic agents and inhibited by α -
adrenergic agents
CATECHOLAMINE RELEASE
 The adrenal medulla, unlike sympathetic
nerves, has no ability to reuptake
discharged catecholamines
 Half-life: 10-30 secs
 Loosely associated with albumin
Catechol-O-Methyltransferase

Monoamine oxidase

VMA
 dihydropteridine reductase

tyrosine hydroxylase

Dihydroxyphenyl

acetic acid

(VMA)
 MAO inhibitors are used to treat
hypertension and depression
 VMA is elevated in patients with tumors of
the adrenal medulla (Pheochromocytoma)
CATECHOLAMINE RECEPTORS

α 1- increase glycogenolysis, smooth muscle

contraction
α 2- smooth muscle relaxation,
vasoconstriction
inhibits lipolysis, renin, insulin, platelet
aggregation
CATECHOLAMINE RECEPTORS
β 1 – increase lipolysis,increase force and rate of
heart contraction
β 2 – increase hepatic gluconeogenesis and
glycogenolysis
increase release of insulin and glucagon
relaxes smooth muscles

Beta receptor genes have no introns and are

homologous to rhodopsin (visual response
protein)
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 α 2 receptors inhibit adenylate cyclase
 α 1 receptors are coupled to processes that alter
intracellular calcium concentrations or modify
phosphatidylinositide metabolism