HORMONES OF ADRENAL MEDULLA

Prof.Dr.Arzu SEVEN

Sympathoadrenal system

Parasympatheticnervous systemwithcholinergic pre andpostganglionic nerves

Sympatheticnervous systemwith cholinergicpreganglionic andadrenergic postganglionicnerves + adrenal medulla

Adrenal medulla is actually an extension of the sympathetic nervous system where choromaffin cells produce catecholamine hormones:

DopamineNorepinephrineEpinephrine(80%)

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

Stress hormones:CatecholaminesGlucocorticoids Growth hormone VasopressinAngiotensin IIGlucagon

Conversion of tyrosine to epinephrine requires 4 sequential steps;

1. Ring hydroxylation2. Decarboxylation3. Side-chain hydroxylation4. N_methylation

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

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

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

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

Catecholamines circulate in plasma in a loose association with albumin

They have an extremely short biological half life (10-30 sec.)

Catecholamines are rapidly metabolized by catechol_O_methyl transferase(COMT) and monoamine oxidase (MAO) to form O_methylated and deaminated metabolites

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

Catecholamines can be classified by their mechanism at action. They act through 2 major classes of receptors ;

α adrenergicβ adrenergic

α

Β

α1

α2

β1

β2

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

α1 receptors are coupled to processes that alter intracellular Ca concentrations or modify phosphatidyl inositide met. (or both)

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