Download Hormones of Adrenal Medulla

Hormones of Adrenal Medulla
The adrenal medulla is considered as neuro-endocrine unit
because it is a part of the sympathetic nervous system & also
produces the catecholamines hormones which are dopamine,
norepinephrine, & epinephrine.
Control of Catecholamines
The release of catecholamines from the adrenal medulla is
stimulated by the low level of catecholamines in the body &
vice versa when the level of catecholamines is elevated it inhibit
its release from the adrenal medulla.
Biosynthesis of Catecholamines
Catecholamines (dopamine, norepinephrine & epinephrine) are
synthesized in the final form from the amino acid tyrosine by
chromaffin cells of the adrenal medulla & stored in these cells to be
released on need. , these cells are also present in some of the
extramedullary tissues such as heart, liver, kidney, gonads,
sympathetic fibers & CNS. However, the main differences
between catecholamines produced by adrenal medulla &
catecholamines produced by the extramedullary tissues are:1- Epinephrine is the main product of the adrenal medulla (80%
of catecholamines produced by adrenal medulla) while
norepinephrine is the main product of extramedullary tissues.
2-Catecholamines produced by the adrenal medulla are
transported by blood circulation to act on other tissues while
catecholamines produced by extramedullary tissues act locally.
The conversion of tyrosine to epinephrine requires four
sequential steps which are:(1) Ring hydroxylation.
(2) Decarboxylation.
(3) Side chain hydroxylation
(4) N-Methylation.
(1) Ring hydroxylation:- It occurs in the cytoplasm of chromaffin
cells, by this step ring hydroxylation of L-tyrosine result in the
formation of L-3,4-dihydroxyphenylalanine (L-dopa),this reaction
is irreversible & is catalyzed by tyrosine hydroxylase enzyme in
the presence of tetrahydropteridine as a cofactor.
Ring hydroxylation is the rate limiting step of catecholamines
biosynthesis.
Tyrosine hydroxylase is regulated in a variety of ways; the most
important mechanism involves feedback inhibition by
catecholamines itself, which compete with tyrosine hydroxylase for
the tetrahydropteridine binding.
Catecholamines cannot cross the blood-brain barrier, hence, in the
brain they must be synthesized locally. In certain CNS diseases
(e.g. Parkinson's disease), there is local catecholamine deficiency in
the brain & treatment is by giving L-Dopa which can readily
crosses the blood-brain barrier & converted into catecholamine
inside the brain.
(2) Decarboxylation: - It occurs in the cytoplasm of chromaffin
cells, by this step decarboxylation of L-dopa result in the formation
of 3,4-dihydroxyphenylethylamine (dopamine), this reaction is
irreversible & is catalyzed by dopa decarboxylase enzyme in
the presence of pyridoxal phosphate as a coenzyme.
Compounds that resemble L-dopa, such as α-methyldopa are
competitive inhibitors of this reaction and can stop the reaction ,
therefore , α-methyldopa is effective in the treatment of some
kinds of hypertension caused by high catecholamine level.
(3) Side chain hydroxylation:- It occurs in the secretion granules
of chromaffin cells, by this step side chain hydroxylation of
dopamine result in the formation of norepinephrine, this reaction
is irreversible & is catalyzed by dopamine β-hydroxylase
(DBH) enzyme in the presence of ascorbate ,copper & fumarate
as coenzymes.
Once norepinephrine is formed it returns back into the cytoplasm
for further step.
(4) N-Methylation:- It occurs in the cytoplasm of chromaffin
cells, by this step N-methylation of norepinephrine results in the
formation of epinephrine, this reaction is irreversible & is
catalyzed
by
phenylethanolamine-N-methyltransferase
(PNMT) enzyme.
The synthesis of PNMT requires induction by high
glucocorticoid hormones concentration (100-fold concentration
gradient over systemic arterial blood) which is present in the
adrenal medulla & this explain why epinephrine is the main
product of adrenal medulla while norepinephrine is the main
product of extramedullary tissues (do not contain high
glucocorticoid concentration).
After formation of norepinephrine & epinephrine they are
stored by secretion granules of chromaffin cells to be released on
need.
Functions of Catecholamines
The main functions of catecholamines especially norepinephrine
& epinephrine are the followings:1- Share in the metabolic response toward trauma.
2-Provide fatty acids as a source of energy.
3-Provide glucose which is important source of energy to brain
by:A-Increase glucose production through stimulation of
glycogenolysis & gluconeogenesis.
B-Inhibit insulin release, therefore, inhibit peripheral glucose
utilization preserving it for the brain.
Transport of Catecholamines
Because catecholamines are hydrophilic, after secretions are
not associated in the plasma with carrier proteins, therefore, they
have short plasma half-life (10-30 seconds).