HORMONES OF ADRENAL MEDULLA
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HORMONES OF ADRENAL MEDULLA
Prof.Dr.Arzu SEVEN
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Sympathoadrenal system
Parasympatheticnervous systemwithcholinergic pre andpostganglionic nerves
Sympatheticnervous systemwith cholinergicpreganglionic andadrenergic postganglionicnerves + adrenal medulla
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Adrenal medulla is actually an extension of the sympathetic nervous system where choromaffin cells produce catecholamine hormones:
DopamineNorepinephrineEpinephrine(80%)
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Adrenal medulla is a specialized ganglion without axonal extension
Its chromaffin cells synthesize , store and release hormonesendocrine organ
Catecholamines are major elements in response to severe stress
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Stress hormones:CatecholaminesGlucocorticoids Growth hormone VasopressinAngiotensin IIGlucagon
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Conversion of tyrosine to epinephrine requires 4 sequential steps;
1. Ring hydroxylation2. Decarboxylation3. Side-chain hydroxylation4. N_methylation
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Tyrosine hydroxylase is the rate limiting enzyme
It functions as an oxidoreductase , with tetrahydropteridine as a cofactor
Feedback inhibition by catecholaminesCompetitively inhibited by tyrosine
derivatives - α_methyltyrosine and by α,α,dipyridyl
Catecholamines can’t cross the blood_brain barrier
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L_Dopa, the precursor of dopamine, readily crosses the blood brain barrier used in the treatment of Parkinson’s disease
Dopa decarboxylase requires pyridoxal phosphate , competetively inhibited by α metil dopa
Dopamine β hydroxylase (DBH) is a mixed function oxidase, uses ascorbate as an electron donor, copper at the active site and fumarate as modulator,conversion occurs in the secretion granule
PNMT is induced by glucocorticoid hormones ,conversion occurs in the cytoplasm
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Catecolamines enter the granule via an ATP_dependent transport mechanism and binds this nucleotide in a 4:1 ratio(hormone:ATP)
NE is stored in these granules, can be N_methylated
Exocytotic release of NE and E are calcium dependent and are stimulated by cholinergic and β_adrenergic agents and inhibited by α_adrenergic agents
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The adrenal medulla, unlike the sympathetic nerves, does not have a mechanism for the reuptake and storage of discharged catecholamines
The epinephrine discharged from the adrenal goes to the liver and skeletal muscle
Very little adrenal NE reaches distal tissues
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Catecholamines circulate in plasma in a loose association with albumin
They have an extremely short biological half life (10-30 sec.)
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Catecholamines are rapidly metabolized by catechol_O_methyl transferase(COMT) and monoamine oxidase (MAO) to form O_methylated and deaminated metabolites
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The concentration of metanephrines or VMA in urine is elevated in > 95% of patients with PHEOCHROMOCYTOMA
Tumor of adrenal medulla NE causes hypertension by activating α_1_adrenoceptors on vascular smooth muscle, and epinephrine increases heart rate by activation β1_adrenoceptors
Hypertension may be paroxysmal and severe, leading to stroke or heart failure
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Catecholamines can be classified by their mechanism at action. They act through 2 major classes of receptors ;
α adrenergicβ adrenergic
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α
Β
α1
α2
β1
β2
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Epinephrine binds and activates both α and β receptors
NE at physiologic concentrations primarily binds to α receptors
The catecholamine receptors are members of the G protein-linked class of receptor
Hormones that bind to β1, γ, β2 receptors activate adenylyl cyclase, whereas hormones that bind to α2 receptors inhibit the enzyme
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α1 receptors are coupled to processes that alter intracellular Ca concentrations or modify phosphatidyl inositide met. (or both)
+2
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